ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.240A>G (p.Val80=) (rs864622281)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001080007 SCV000259960 likely benign Hereditary nonpolyposis colorectal neoplasms 2020-11-23 criteria provided, single submitter clinical testing
Counsyl RCV000410492 SCV000489318 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-09-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000565482 SCV000669884 likely benign Hereditary cancer-predisposing syndrome 2015-06-12 criteria provided, single submitter clinical testing Rarity in general population databases (dbSNP, ESP, 1000 Genomes);Synonymous alterations with insufficient evidence to classify as benign
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000855621 SCV000695813 likely benign not specified 2019-08-29 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000588097 SCV000805865 likely benign not provided 2018-01-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000410492 SCV001300594 uncertain significance Hereditary nonpolyposis colorectal cancer type 5 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Color Health, Inc RCV000565482 SCV001347028 likely benign Hereditary cancer-predisposing syndrome 2016-02-24 criteria provided, single submitter clinical testing
GeneDx RCV000588097 SCV001846891 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354250 SCV001548814 uncertain significance Lynch syndrome no assertion criteria provided clinical testing The MSH6 p.Val80= variant was not identified in the literature nor was it identified in COGR, Cosmic, MutDB, UMD-LSDB, Zhejiang Colon Cancer Database, Mismatch Repair Genes Variant Database, and Insight Hereditary Tumors Database. The variant was identified in dbSNP (ID: rs864622281) as “With Likely benign allele”, in ClinVar (classified likely benign by Invitae, Counsyl and Ambry Genetics and uncertain significance by Laboratory Corporation of America), Clinvitae (2x) and the Genome Aggregation Database (Feb 27, 2017) in 2 of 30730 control chromosomes (frequency: 0.00007). It was observed in the following populations: African in 1 of 8664 chromosomes (frequency: 0.0001) and European Non-Finnish in 1 of 14844 chromosomes (frequency: 0.00007), but not in the Other, Latino, Ashkenazi Jewish, East Asian, Finnish and South Asian populations. The p.Val80= variant is not expected to have clinical significance because it does not result in a change of amino acid. The variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. This variant is classified as a variant of uncertain significance.

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