ClinVar Miner

Submissions for variant NM_000179.3(MSH6):c.2818G>T (p.Ala940Ser)

gnomAD frequency: 0.00003  dbSNP: rs772978164
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000460082 SCV000551234 likely benign Hereditary nonpolyposis colorectal neoplasms 2023-12-27 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000580547 SCV000685326 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-21 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 940 of the MSH6 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 10/281986 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000580547 SCV002749491 likely benign Hereditary cancer-predisposing syndrome 2023-10-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics RCV003463940 SCV004195599 uncertain significance Endometrial carcinoma 2024-03-27 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004001849 SCV004836310 uncertain significance Lynch syndrome 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces alanine with serine at codon 940 of the MSH6 protein. Computational prediction tool suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 10/281986 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004525934 SCV005040475 uncertain significance not specified 2024-03-02 criteria provided, single submitter clinical testing

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