Submissions for variant NM_000179.3(MSH6):c.628-7C>T

dbSNP: rs373129248

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000444664	SCV000527400	likely benign	not specified	2017-07-04	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001082338	SCV000561478	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-09-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589714	SCV000695920	uncertain significance	not provided	2016-05-25	criteria provided, single submitter	clinical testing	Variant summary: The MSH6 c.628-7C>T variant involves the alteration of a non-conserved intronic nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing and the elimination of an ESE binding site, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC with an allele frequency of 1/117788 (frequency 0.0000085), which does not exceed the estimated maximal expected allele frequency for a pathogenic MSH6 variant of 1/7037 (0.0001421). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories. Because of the absence of clinical information and the lack of functional studies, the variant has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available.
Color Diagnostics, LLC DBA Color Health	RCV001525063	SCV001735065	likely benign	Hereditary cancer-predisposing syndrome	2020-08-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003912717	SCV004735190	likely benign	MSH6-related condition	2022-06-27	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).