Submissions for variant NM_000179.3(MSH6):c.2958C>T (p.Thr986=)

dbSNP: rs757866392

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000205677	SCV000260465	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-11-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000491625	SCV000580226	likely benign	Hereditary cancer-predisposing syndrome	2016-03-08	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.
Color Diagnostics, LLC DBA Color Health	RCV000491625	SCV000685338	likely benign	Hereditary cancer-predisposing syndrome	2016-11-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587841	SCV000695833	likely benign	not specified	2024-10-07	criteria provided, single submitter	clinical testing	Variant summary: MSH6 c.2958C>T alters a non-conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.4e-05 in 220130 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2958C>T in individuals affected with Hereditary Nonpolyposis Colorectal Cancer/Lynch Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 220147). Based on the evidence outlined above, the variant was classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284658	SCV001470559	likely benign	not provided	2020-04-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001284658	SCV001862330	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003997615	SCV004839078	likely benign	Lynch syndrome	2023-08-28	criteria provided, single submitter	clinical testing