General

Purpose

The software release notes describe the changes in the device upon market release.

Installation

Given Moon is cloud-based software, no installation is required.

Customer Support

If you require assistance, please do not hesitate to contact support at moon@invitae.com

Terms and Conditions

The use of the device is subject to the term and conditions provided on the log-in screen and within the device.

Software release notes

Moon version 4.0.2

26 September 2022 • 6fb95b3, c0a5842

Features

• Only laboratory admins will be able to initiate a payment [MOON-453]

Annotation sources

The following databases will be updated to their most recent version:

• ClinVar: 10-09-2022 (IPTR-175)

• Mastermind: 22-07-2022 (IPTR-175)

• Apollo: 26-09-2022 (IPTR-175)

• ClinGen: 12-09-2022 (IPTR-175)

Impact

Update of annotation sources can have an impact on performance of automated pipeline of the device. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 4.0.2 (release date 26-09-2022).

Moon version 4.0.1

20 June 2022 • 3eafe9a1028583ede46403301d6c743e666dc076, 951ab6b7acd1908d584c383c517808b401bbade6

Features

• Variant ID field from the VCF is now also displayed in the Moon API output (MOON-489)

Bug fixes

• Fix for ClinVar import: in 4.0.0, some ClinVar classifications (including 0.2% of LP/P classifications) were missing in Moon variant cards (MOON-497)

• Fix for ACMG PS3 not being visible in the UI (MOON-504)

Annotation sources

The following databases were updated to their most recent version:

• ClinVar: 2022-06-06 (MOON-498)

• Mastermind: 2022-04-02 (MOON-420)

Impact

Update of annotation sources can impact selection of variants for the Shortlist. Issue MOON-497 caused 318 variants to not have an ClinVar annotation displayed by Moon. Of these, 289 variants would have been annotated as LP/P (0.2% of all LP/P ClinVar variants). The ClinVar annotations are leveraged to improve prioritisation of variants in the automated pipeline in case no KB or InvitaeKB classifications are available. Therefore, the absence of these annotations could potentially have caused an impact on samples analysed with Moon 4.0.0. In case of questions, please contact support.

User Documentation

The manual was updated to version 4.0.1 (release date 20-06-2022).

Moon version 4.0.0

1 May 2022 • 87c5011, ef88598

New features

• Addition of a Quality page for SV/CNV input files (MOON-277)

• Addition of a Filter view for SV/CNVs (MOON-254; MOON-416; MOON-441)

• Annotation and analysis of BND calls in automated pipeline and Filter view (MOON-188)

• Addition of gnomAD SV as annotation source for deletions and duplications (MOON-211)

• Updates to family segregation filtering in SV/CNV pipeline (MOON-259)

• Addition of SV/CNV to exon-level visualisation in the SV/CNV genome browser (MOON-275)

• Compound heterozygosity of a carrier SNV with an SV/CNV variant is now also indicated for the variant in the Carrier tab (MOON-99)

• Support detection of SV/CNVs overlapping non-protein coding genes; change requirement for exonic overlap in automated SV/CNV pipeline (MOON-257)

• Display known SV/CNV syndromes in the SV/CNV Shortlist and variant cards (MOON-411)

• Add zygosity-inheritance filtering for SV/CNVs affecting single genes (MOON-216)

• Allow to upload gzipped VCF files for SV/CNV input (MOON-415)

• Annotate 'updated' label if differences in reanalysis results for SVs (MOON-412)

• Add SV/CNVs to the Shortlist download (MOON-414)

• Addition of ACMG classification support in the KB (MOON-33)

• Addition of Moon favicon (MOON-409)

• Addition of an API endpoint for updating Patient information (MOON-413)

Bug fixes

• Reactivate DGV filter in SV/CNV pipeline. DGV was not used for filtering in previous Moon versions (MOON-299)

• Reactivate support for upload of SV files from NexusClinical (MOON-415)

• Fix for incorrect de novo annotation SV/CNVs if parents have no SV/CNV data uploaded to Moon (MOON-316)

• Fix for gene annotation for inversions. For phenotype matching in the automated pipeline, only genes overlapping inversion breakpoints considered (MOON-212)

• Fix for HPO checklist for shortlisted SNV variants showing HPO matches for disorders caused by mutation in the gene of relevance, but other than the annotated disorder in Moon (MOON-407)

• Fix location of the ‘Show more’ button in the HPO list on the Shortlist screen (MOON-408)

• Change the Alamut Visual (Plus) search to only the genomic position (removing Ref and Alt) for insertions and deletions (MOON-327)

• Fix HPO mining error (MOON-406)

• Fix automated removal of spaces in the Referral note (MOON-437)

Annotation sources

• The following databases were updated to their most recent version:

  • ClinVar: 2022-04-12 (MOON-419)

  • Apollo: 2022-04-21 (MOON-417)

  • InvitaeKB: 2022-04-20 (MOON-418)

  • SpliceAI: 2022-04-21 (extension of intronic SpliceAI annotations) (MOON-421; MOON-436)

  • ClinGen regions: 2022-03-31 (MOON-289)

Impact

Update of annotation sources can impact selection of variants for the Shortlist. Updates to the automated SV pipeline (MOON-188; MOON-211; MOON-259; MOON-257; MOON-216; MOON-299; MOON-212) contribute to overall filtering and ranking of SV variants in the Shortlist. Addition of the Filter view for SVs, allows to review all SVs in the inputted sample, irrespective of any filters used in the automated pipeline. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 4.0.0 (release date 1-05-2022).

Moon version 3.6.0

18 February 2022 • 041c06c, 5b2b5f5

New features

• Addition of EVE predictions (2021-11-17) as annotation (Frazer et al., 2021), contributing to variant ranking in the Shortlist. EVE scores are highlighted in red if the value is > 0.762 (PPV80 threshold based on internal testing) (MOON-343)

• Warning for non-existing/recognised genes when adding/editing a Panel (MOON-242)

• Warning for non-existing/non-recognised genes in the Genes filter in the Filter view (MOON-235)

• Possibility to open a variant in Alamut Visual Plus via the position menu, or c. notation in the variant card (MOON-327)

• Newsletter is now displayed in Moon after a new version is released and the most recent Newsletter can be reviewed at any time through the help menu (MOON-348)

• Filter view now allows to only display variants with an associated Apollo disorder annotation (MOON-208)

• On the Samples overview screen, it is now also possible to filter samples based on not being part of a Project (MOON-392)

Bug fixes

• Fixed the Filter set error page in case an active Filter set contained a panel that had already been removed from the account (MOON-342)

• Order of HPOs is now consistent over Patient info screen, Shortlist screen and variant cards (MOON-317)

• Fix for annotating mitochondrial variants if chromosome is indicated as ‘chrM’ in the VCF (MOON-335)

• Fixed genome browser layout, making sure the full gene is always visible (MOON-347)

• Structural fix for KB export when KBs are not shared, after previous temporary fix (MOON-297) (MOON-297)

• Fix to allow Stripe payments on US server (MOON-352)

• Variants with multiple gene-specific classifications are now annotated with the most severe InvitaeKB classification (MOON-253)

• Fix for incorrectly retaining compound heterozygous variants in the Shortlist despite low phenotype overlap, if one of the variants has a loss of function effect, and is annotated with a disorder that has a loss of function pathogenic mechanism (MOON-378)

• Correction of the Ref and Alt in the Alamut Visual link, now including the genomic Ref and Alt instead of coding Ref and Alt (MOON-383)

• Improvement of variant ranking in Shortlist (MOON-391)

• Fix for incorrect language detection in Referral notes. Supported languages for HPO extraction are English, Dutch, French, Spanish, Portuguese, Swedish and Italian (MOON-397)

Annotation sources

• The following databases were updated to their most recent version (MOON-344; MOON-345; MOON-346; MOON-386; MOON-395)

  • ClinVar: 2022-02-05

  • Mastermind: 2022-01-06

  • Apollo: 2022-02-14

  • InvitaeKB: 2022-01-23

  • SpliceAI: 2022-02-11

Impact

Update of annotation sources can impact selection of variants for the Shortlist. EVE annotation (MOON-343) and the update to the ranking algorithm (MOON-391) contribute to overall ranking of variants in the Shortlist. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.6.0 (release date 18-02-2022).

Moon version 3.5.1

6 December 2021 • b270ca8

Bug fixes

• Fix for HPO extraction from referral notes for non-English text, with empty lines at beginning or end of the inputted text (MOON-71)

• Fix for use of annotation source InvitaeKB (GRCh37 samples only). In Moon 3.5.0, version 2021-06-04 was still in use. This has now been fixed in order to use version 2021-10-06. Variants classified as LB/B by Invitae based on this latest version of the data source, will now be filtered out of the automated analysis (if not overruled by a classification in the lab’s KB). Variants with LP/P classifications will be less stringently assessed for inclusion in the Shortlist based on classifications in this most recent version as of Moon 3.5.1 (MOON-306).

Impact

Update of annotation sources can have an impact on performance of automated pipeline of the device given use of Invitae KB classifications for selecting variants for the shortlist. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.5.1 (release date 06-12-2021).

Moon version 3.5.0

23 November 2021 • commit 6c77d9a

New features

• Addition of SpliceAI annotation for variants within disease-associated genes located within exons or 200 nt flanking intronic regions and covering SNVs and 1-2 nt indels. Use of SpliceAI annotations in the automated pipeline, and possibility to filter on SpliceAI annotation in the Filter view (MOON-300)

• HPOs can automatically be extracted from a Referral note on the Patient info screen (MOON-71)

• Addition of gnomAD MT as annotation source for MT variants. This annotation is now used during automated analysis of MT variants (MOON-155).

• KB functionality:

  • All variants in the KB now have a source indication, which can be seen and changed in the KB UI (MOON-313)

  • The KB UI opens in a new tab when clicking the KB icon for a variant (MOON-320)

  • After adding a Shortlisted variant to the KB, the KB icon remains visible with an indication that the variant has been added to the KB (MOON-319)

  • In the Shortlist, a message is shown if there were updates to the KB classification of currently shortlisted variants. The sample needs to be reanalysed to display this new annotation, and take advantage of the updated KB classifications during analysis (MOON-323)

  • Performance improvements for retrieving the KB trough the API (MOON-311)

  • Added the possibility to request the KB logs through the API (MOON-312)

• Improved filtering for variants expected to cause loss-of-function based on effect and location within the gene and for which the annotated disorder is known to be caused by a loss of function pathogenic mechanism (MOON-41)

• De novo splice variants can be selected for the Shortlist even if splice predictions are not significant, although other requirements (eg. frequency, effect, phenotype match) still need to be met (MOON-98)

• The Segregation filter in the Filter view now also provides the option to filter for De novo, Paternal, Maternal or biparentally inherited variants (MOON-321)

• Downloads:

  • Addition of a ‘Parental origin’ column to all downloadable files (options: maternal, paternal, biparental, de novo, inconclusive)(MOON-315)

  • CSV Shortlist download: Addition of the Shortlist category in which the variant was reported (SNV, Carrier, Manually filtered)(MOON-338)

• Use of MANE for translation of ENSTs to NM IDs for GRCh38. For GRCh37 samples, a lift-over from MANE is used to improve ENST to NM translation (MOON-240)

• Addition of the possibility to remove applied Filter sets from the Report. Removing a Filter set from the report is logged in the Sample logs (MOON-331)

• Update of the list of common pathogenic variants, which are also annotated and considered during analysis in Moon, despite having a gnomAD frequency > 2% (addition of NM_000155.2(GALT):c.-119_-116delGTCA and NM_000140.5(FECH):c.315-48T>C) (MOON-333)

• Digitally signing or authorising reports is now logged in Sample logs (MOON-10)

• Samples are now searchable based on HPO IDs in the samples search box (MOON-161)

• Files with .VCF as extension are now also accepted for upload (in addition to .vcf files) (MOON-310)

• Based on the input HPOs, only 10 suggestions are shown anymore (MOON-314)

• Haplotypes/patch chromosomes are not annotated or considered during analysis (MOON-196)

• In the Filter view, the exclusion reason for Carriers is now shown as “Shortlisted by Moon, carrier” (MOON-322)

• When signing up for Moon, a disclaimer is added to make sure users want to create a new lab instead of joining an existing lab (MOON-318)

• 2FA setup and login in Moon are now improved (MOON-326)

• Update to sample upload allowing parallel file uploads and improved display of upload status on upload screen (MOON-328)

Annotation sources

• The following databases were added or updated to their most recent version (MOON-300; MOON-303; MOON-304; MOON-305; MOON-306)

  • ClinVar: 2021-10-16

  • Mastermind: 2021-10-12

  • Apollo: 2021-10-20

  • InvitaeKB: 2021-10-06

  • SpliceAI: generated by Invitae with SpliceAI code version 1.3.1 (2021-10-20), unmodified; Max distance: 50

Bug fixes

• Link to Alamut Visual based on chromosomal position now also includes the Ref and Alt of the variant. Changed links to Alamut Visual when clicking c. notations in the variant cards (genome build is removed, point versions of RefSeq transcripts might still need to be manually added in the Alamut search field) (MOON-308)

• Fix for filtering out variants based on gnomAD hemizygotes > 0 for genes in which variants are only disease causing in heterozygous state (MOON-226)

• In the Filter view, the link directly to the Comments section in the variant cards is fixed (MOON-302)

• Fix for incorrect (previous) .CSV exports (MOON-309)

• Automatically generated report notes:

  • variants reported in literature (based on Mastermind) are no longer indicated to be 'novel' (MOON-19)

  • fix for incorrect ‘de novo’ indication in report notes (MOON-156)

• Fix for error when no gender was provided as Patient info (MOON-377)

Impact

Implementation of MOON-41, MOON-98, MOON-300 is expected to reduce the number of false negatives and potentially increase the number of shortlisted variants. MOON-155 impacts filtering of MT variants in the automated analysis. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.5.0 (release date 23-11-2021).

Moon version 3.4.0

28 June 2021 • commit 1115d2a, 093f8cfbb5e482ed06db6d6e87528c53ad086ab4

New features

• Addition of a case repository feature in Moon’s UI (MOON-47, MOON-281)

• The search field in Moon now also allows to search for genes that are shortlisted in the SV/CNV tab (MOON-234)

• Moon’s API for updating or adding variants to the internal knowledge base has now been improved (MOON-282, MOON-288)

• Moon’s system security has been further enhanced, including password policy and server time-out updates (MOON-269, MOON-285, MOON-287, MOON-290, MOON-291)

• Moon now supports generic authenticator apps in addition to Authy for 2FA (MOON-294)

• You can now have the possibility to disable 2FA once enabled (MOON-292)

• You can now assign samples back to “Nobody” after initially assigned to someone (MOON-293)

Annotation sources

• The following databases were updated to their most recent version (MOON-110, MOON-218)

  • ClinVar: 2021-06-09

  • Mastermind: 2021-04-02

  • Apollo: 2021-06-08

  • InvitaeKB: 2021-06-04

Bug fixes

• Fix to SV/CNV shortlist indicating "Moon could not find any relevant structural variants" as soon as a SV/CNV VCF is uploaded and irrespective of whether the analysis actually included the SV/CNV file (MOON-111)

• Fix to VCFs containing haploid calls on X for male samples are incorrectly handled by Moon, leading to incorrect gender prediction (MOON-286)

• Fix to part of ClinVar and Mastermind data not shown in the Genome browser (in 347 out of 394289 transcripts) (MOON-295)

• Fix to missing internal KB annotations in both the automated analysis and UI labels (MOON-297). Bug introduced with the last Moon release in May 3rd.

• Fix to no responsive comment text field in variant cards (MOON-298)

Impact

Fix for MOON-282 has an impact on Moon’s gender prediction, although this does not impact the analysis. MOON-297 has an impact on Moon’s automated analysis: since Moon uses the internal KB annotations to rank and prioritise variants in the automated pipeline, this bug can potentially have caused performance issues on samples analysed after May 3rd. This has now been fixed. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.4.0 (release date 28-06-2021).

Moon version 3.3.4

27 April 2021 • commit be49c7a

Bug fixes

• Performance optimisation, allowing for 15 min time savings for WGS analysis (MOON-276)

• Nexus files with SV/CNV calls can now be imported regardless of their format (MOON-279)

• Checklists are now correctly reflecting matches with parent and grandparent HPO terms. All matches up to 2 levels up and down in the HPO as compared to the input HPO terms are now checked in the variant card (MOON-273)

• Corrected the exclusion filter in the Filter view, for variants excluded based on ‘Benign/Likely benign on ClinVar or in InvitaeKB or in KB’ (MOON-262)

• Fix for allowing to conduct a family analysis in which a sample indicated as family member has previously been analysed as proband (MOON-280)

Impact

Release testing did not indicate impact on performance or safety of the device. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.3.4 (release date 27-04-2021).

Moon version 3.3.3

24 March 2021 • commit 702f9ca

New features

• Addition of an integrated SV/CNV genome browser (MOON-163)

• Improvements to the automated pipeline:

  • Variants with a Benign/Likely Benign classification in InvitaeKB are now filtered out from the automated pipeline (MOON-246)

• Additions/improvements to Filter view functionality:

  • Introduction of ‘Exclusion’ filter option, allowing to filter variants based on Moon’s reason for exclusion from the Shortlist (MOON-134)

  • Addition of ‘Non coding transcript exon’ option to the Effects filter, allowing more specific filtering for variants in non-protein coding genes (MOON-179)

  • Addition of an ‘Export’ button to download the list of variants resulting from a given combination of filter settings, as a .txt csv file (MOON-201)

  • Extension of the Frequency filter, allowing to lower the gnomAD/Diploid frequency below 0.1% and to set any desired frequency threshold with the slider or free input (MOON-202)

• Improvements/additions to the UI:

  • The version of the annotation sources used by Moon at the time of analysis is now also included in the PDF report as an Appendix (MOON-123)

  • HPO lists are now expandable in case of a large number (>10) of input HPO terms (MOON-150)

  • Clickable HP IDs are now also shown next to the HPO terms in the Shortlist and PDF report (MOON-243)

  • The c.notation of variants in transcripts that have a RefSeq ID, now link out to Alamut Visual, allowing to immediately open the specific mutation in Alamut Visual (MOON-239)

• Added support for the option to share Knowledge Bases among labs using the same server (MOON-189)

• Samples analysed by the Autopilot now have the lowest priority (MOON-207)

Annotation sources

• The following databases were updated to their most recent version (MOON-110, MOON-218)

  • ClinVar: 2021-03-02

  • Mastermind: 2021-01-02

  • Apollo: 2021-02-26

  • InvitaeKB: 2021-02-25

  • HPO: 2021-02-08

Bug fixes

• Fix for possibly incorrect gnomAD frequency annotations in Moon for variants at positions where there are multiple variants with the same Alt but different Ref alleles in gnomAD (MOON-31, MOON-138)

• Samples and SV/CNV VCF files are not allowed to be removed/deleted anymore during analysis (MOON-87, MOON-108)

• Patient info screen HPO input is now limited to HPO terms from the ‘Phenotypic abnormality’ branch (MOON-160)

• Fix for MT variants with assigned GRCh37/38 build in the KB. Moon now makes sure MT classifications are used in all circumstances, regardless of the SNV VCF’s genome build (MOON-191)

• Fix for high quality variants being excluded for 'Low quality' due to high DP (MOON-213)

• Fix for Error page displayed when clicking the ‘My samples’ button when on the ‘New samples’ upload page (MOON-214)

• Following the update of the Decipher genome browser to GRCh38 (version v11.0 - December 9th 2020), Decipher links are now only available for GRCh38 samples in Moon (MOON-215)

• The order of the variants in the report now always corresponds with the order of variants in the Report tab in the Moon UI (MOON-220)

• Moon can now detect compound heterozygosity when observing two 0/1 calls with the same position in the VCF (MOON-223)

• Fix for the mismatch between the API documentation for siblings (upload as sibling) and the UI sibling options (brother/sister on patient info screen) which caused seemingly wrong relations to be displayed on the Patient info screen (MOON-230)

• Fix for display of variants with long Ref/Alt alleles that were truncated in the UI (MOON-232)

• The link to the HPO page from the Patient info screen is fixed (MOON-244)

Impact

Fixes for MOON-31, MOON-191 and MOON-223 have an impact on variant annotation in both the automated pipeline and filter view and can therefore impact performance. Fix for MOON-213 and addition of MOON-246 have an impact on the automated pipeline and might change Shortlist results. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.3.3 (release date 24-03-2021).

Moon version 3.3.2

14 December 2020 • commit 786c61c

New features

• Use of gnomAD v3.1 for frequency annotations in GRCh38 samples, including the possibility to click out to the gnomAD v3.1 webpage from within Moon (MOON-96)

• Additions to Autopilot functionality (MOON-116, MOON-197):

  • The Autopilot is now also able to flag cases with updated variant classifications from the lab’s internal Knowledge base, ClinVar, or both, based on user preferences.

  • As part of the Autopilot settings, users can now decide to only compare updates within the top n variants in the Shortlist.

  • Samples with updates after an Autopilot reanalysis can now be found in the Autopilot page for all users.

• User interface improvements:

  • Primary findings in MT genes are now displayed in a separate Shortlist tab, which will only be displayed in case of Shortlisted variants in MT genes (MOON-169)

  • Knowledge Base entries now have a “Source” field to indicate the origin of an entry (MOON-133). The source can be indicated when uploading Knowledge Base variants through the API.

• The API output for variants now contains a “in_report” field to indicate whether a variant has been reported (true/false), per analysis (MOON-114)

• Moon now allows BND calls (translocations) in SV/CNV VCFs (MOON-183). These BND calls are however not yet annotated or included for the interpretation.

Annotation sources

• The following databases were updated to their most recent version (MOON-187, MOON-172, MOON-96)

  • ClinVar (GRCh37 and GRCh38) (2020-11-21)

  • Mastermind (GRCh37 and GRCh38) (2020-10-02)

  • Apollo (2020-11-26)

  • InvitaeKB (GRCh37 only) (2020-12-02)

  • gnomAD (GRCh38): 3.1

• The rest of annotations have maintained the same version as in the previous release:

  • dbNSFP: 4.0

  • dbSNP: 151

  • dbscSNV: 1.1

  • RefSeq: 37/38

  • gnomAD (GRCh37): 2.1.1

  • HPO: 2019-02-12

  • DGV: 2016-03-01

  • dbVar: 2019-07-07

  • Mitomap: 2019-01-14

  • Mitimpact: 2.9.1

Bug fixes

• Fix to avoid the analysis of samples uploaded through the API before the genome build is determined (MOON-153)

• Fix to ClinVar and Mastermind tooltips in the Genome browser showing Ref instead of Alt allele (MOON-170)

• Fix missing gene ENSG IDs in Apollo, impacting disorder annotations in Moon (MOON-180). Genes impacted could have lead to false negative results in the automated analysis of previous Moon versions:

  • Both for GRCh37 and GRCh38 analyses: TERC, SNORD118, MT-TD, MT-TS1, MT-TG, MT-TS2, MIR204, MT-TW, MT-TP, MT-TA, MT-TL1, CCNQ, MT-TQ, MIR96, MT-TF, MT-TM, MIR184, MT-TT, MT-TC, H19, NR2E3, MT-TY, MT-TN, MT-TE, MT-TL2, MT-TV, RNU4ATAC, MT-TR, MIR140, TRAC, RNU12, LINC00505, MIR17HG, MT-TK, MT-TH, MT-TI. Additionally, only for GRCh37 analyses: SRD5A2, NEFL, MAP3K14, PADI6 and RMRP.

• Fix for the exclusion filter of MT variants in the Filter view, which could be incorrectly shown as ‘Shortlisted by Moon’ even if not shortlisted (MOON-194)

• Fix to restore the running of Autopilot analyses (MOON-200).

Impact

Fix of MOON-180 has an impact on disorder annotations in both the automated analysis and filter view. Fix of MOON-200 has an impact on automated reanalysis. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.3.2 (release date 14-12-2020).

Moon version 3.3.1

6 September 2020 • commit b9acc16

Bug fixes

• Fixed issue with annotation sources without Grch38 version (MOON-164)

Impact

Release testing did not indicate impact on performance or safety of the device. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.3.1 (release date 06-09-2020).

Moon version 3.3.0

2 September 2020 • commit 47d98b0

New features

• Improvements to automated variant filtering and ranking: Addition of InvitaeKB variant classifications (Nykamp et al., 2017) as a new annotation source (MOON-137)

• Addition of functional protein annotations to the Genome browser (MOON-154)

• Improvements to family analysis:

  • Addition of an automated Family relations check feature for confirmation of relationships between family members (MOON-144)

  • Addition of the family information provided through the patient info screen (family relations and status) to the pedigree in variant card and PDF report (MOON-135)

• Ability to retrieve HPO checklists through the API (MOON-140)

• Updates to the automated report note:

  • Addition of chromosomal location, gnomAD frequency for all variants including variants in ClinVar/KB, and RefSeq ID to the automated report notes (MOON-88)

  • It is now possible to indicate the language in which the automated report notes should be generated within an analysis (English/Dutch) (MOON-149)

• Removal of the “More variants” button: The full list of variants in the shortlist SNV tab is now directly displayed (MOON-148)

• Addition of ENST transcript ID, RefSeq ID and family information fields in the All rare variants download file (MOON-151)

Annotation sources

• The following databases were updated to their most recent version (MOON-141/137)

  • Clinvar (2020-08-10)

  • Mastermind (2020-07-10)

  • Apollo (2020-08-18)

  • InvitaeKB (2020-08-20)

Bug fixes

• The timings in the Time Machine menu and the timing of the selected analysis are now synchronised (MOON-21)

• Samples with a dot in their name can now be found using the Search field on Samples screen (MOON-30)

• UCSC and gnomAD links referring to GRCh37 pages for GRCh38 samples in the PDF report are now fixed and correctly refer to GRCh38 pages (MOON-85)

• The links to OMIM, UCSC and Mitomap from the dropdown menus next to the gene name or variant location now work correctly again (MOON-89, MOON-118)

• Fix to avoid the removal of variants defining changes at the same position but with different Refs than KB variants updated through API (MOON-130)

• Initiator_codon effect is now fixed and initiator_codon variants are now considered truncating, just like start_lost variants (MOON-132)

• Fix to restore Autopilot notifications within lab accounts with autopilots set with a time frame of 0 (MOON-139)

• Exclusion filter indicated as 'Shortlisted by Moon' in Filter view for variants that were not listed in the Shortlist are now fixed (MOON-142)

Impact

Addition of the InvitaeKB as additional annotation source might impact performance similar to other annotation sources containing known variant classifications. Fix of MOON-132 has an impact on selection of initiator_codon variants in both the automated analysis and filter view.
Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.3.0 (release date 02-09-2020).

Moon version 3.2.4

6 April 2020 • commit b450066

New features

• Filter Sets: Possibility to save a set of filters in the Filter view, and apply these on future samples (ticket MOON-70)

• Error handling: improved notifications in case of analysis failures (MOON-112)

• Additions to the API to allow removal of KB entries, add the ability to specify a source for each KB entry (MOON-109)

• Effect filter in Filter view: Both ‘non-synonymous’ coding and ‘splicing’ are now selected as Effect with default filter settings (ticket MOON-124)

Annotation sources

• The following databases were updated to their most recent version

  • Clinvar (2020-03-16) (MOON-125)

  • Mastermind (2020-01-01) (MOON-107)

  • Apollo (2020-03-20) (MOON-125)

Bug fixes

• Fix to allow download of the entire KB with a single API call (MOON-128)

• Fix for updating different variants at the same position when create_or_update is called for a KB variant (MOON-129)

Impact

Release testing did not indicate impact on performance or safety of the device. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.2.4 (release date 06-04-2020).

Moon version 3.2.3

3 February 2020 • commit d4273b0

Bug fixes

• ClinVar annotations not shown for variants with Conflicting interpretations on ClinVar (MOON-119)

Impact

Release testing did not indicate impact on performance or safety of the device. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.2.3 (release date 03-02-2020).

Moon version 3.2.2

16 December 2019 • commit 18b131e

Annotation sources:

• The following database was updated to the most recent version (ticket MOON-104)

  • Apollo (2019-12-12)

Impact

Release testing did not indicate impact on performance or safety of the device. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.2.2 (release date 16-12-2019).

Moon version 3.2.1

10 December 2019 • commit a88632f

New features:

• Urgent samples: Added the possibility to prioritise samples for analysis on the Patient info screen (ticket MOON-93)

Annotation sources:

• The following database was updated to the most recent version (ticket MOON-102)

  • ClinVar (GRCh37 and GRCh38) (2019-12-02)

Bug fixes

• Samples cannot be removed anymore during analysis (MOON-87)

• Improvement of the selection of the most severe effect in case ‘synonymous_coding’ is one of the possible effects (MOON-90)

• Correction of links for SV/CNVs in the shortlist for GRCh38 samples (ticket MOON-95)

• ClinVar classification is now also annotated for variants with Conflicting interpretations of pathogenicity in addition to a risk factor annotation (MOON-100)

• Genome build of SV/CNV files is now correctly recognised in the UI (MOON-103)

Impact

Release testing did not indicate impact on performance or safety of the device. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.2.1 (release date 10-12-2019).

Moon version 3.2.0

7 October 2019 • commit f06b64f

New features:

• Addition of support for annotation and analysis of GRCh38 VCF files with the following versions of annotation sources (ticket MOON-79):

  • ClinVar: 2019-10-03

  • dbNSFP: 4.0

  • dbSNP: 151

  • dbscSNV: 1.1

  • Apollo: 2019-10-06

  • RefSeq: 38

  • gnomAD: 2.1.1

  • HPO: 2019-02-12

  • KB: 2019-10-06

  • DGV: 2016-03-01

  • dbVar: 2019-07-07

  • Mitomap: 2019-01-14

  • Mitimpact: 2.9.1

  • Mastermind: 2019-09-27

• Addition of a Genome Browser functionality for SNVs (ticket MOON-80)

• Prediction of gender based on the VCF file, shown on the patient info screen (ticket MOON-83)

• Bug fixes:

  • Correction in the annotation of the number of X-linked heterozygotes on gnomAD (ticket MOON-15)

  • Improvements in handling variants with multiple (superfluous) ALT alleles in the VCF (tickets MOON-17/18)

  • Correction of 0% gnomAD frequency annotation for variants with multiple Alt alleles (ticket MOON-20)

  • Improvements in handling haploid GT fields in the VCF (ticket MOON-22)

• The following GRCh37 databases were updated to their most recent version (ticket MOON-78)

  • ClinVar: 2019-10-03

  • dbNSFP: 4.0

  • dbSNP: 151

  • Apollo: 2019-10-06

  • gnomAD: 2.1.1

  • dbVar: 2019-07-07

  • Mastermind: 2019-09-27

Impact

Release testing did not indicate impact on safety of the device. New features are intended to further lower existing risk of false positive or false negative results in the automated pipeline. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.2.0 (release date 07-10-2019).

Moon version 3.1.2

19 July 2019 • commit c47740e

New features:

• The following databases were updated to their most recent version (ticket MOON-23)

  • Apollo (2019-07-19)

  • ClinVar (2019-07-01)

Impact

Release testing did not indicate impact on performance or safety of the device because new features are related to database updates. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.1.2 (release date 19-07-2019).

Moon version 3.1.1

25 June 2019 • commit 182d3cd

New features:

• CE IVD marking on the European market

• Bug fixes:

  • Improved handling of variants with multiple Alt alleles (ticket MOON-2)

  • Improved handling of known (likely) pathogenic multi-allelic sites in automated analysis (ticket MOON-6)

  • Updated the list of common pathogenic variants (ticket MOON-16)

Impact

Release testing did not indicate impact on performance or safety of the device because new features are related to visualisation and workflow improvements. Users are recommended to conduct their own impact assessment. In case of questions, please contact support.

User Documentation

The manual was updated to version 3.1.1 (release date 25-06-2019).