Submissions for variant NM_000179.3(MSH6):c.2919T>C (p.Gly973=)

dbSNP: rs1057522150

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001205054	SCV001376290	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2021-12-17	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 936284). This variant has not been reported in the literature in individuals affected with MSH6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 973 of the MSH6 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MSH6 protein.
Ambry Genetics	RCV002436789	SCV002748389	likely benign	Hereditary cancer-predisposing syndrome	2019-01-11	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002469351	SCV002765951	likely benign	not specified	2022-11-19	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV002436789	SCV004357681	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-26	criteria provided, single submitter	clinical testing	This variant is located in the MSH6 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MSH6-related disorders in the literature. This variant has not been identified 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.