Submissions for variant NM_000179.3(MSH6):c.3456A>G (p.Val1152=)

dbSNP: rs750998416

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000417896	SCV000520396	likely benign	not specified	2017-06-08	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	RCV001088478	SCV000561445	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-04-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000572401	SCV000662401	likely benign	Hereditary cancer-predisposing syndrome	2016-02-12	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	RCV000587235	SCV000695867	likely benign	not provided	2017-08-09	criteria provided, single submitter	clinical testing	Variant summary: The MSH6 c.3456A>G (p.Val1152Val) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect binding of any ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/121342 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic MSH6 variant (0.0001421). This variant has been reported in one patient with ovarian cancer who also carries MSH6 c.3083C>A (p.Ser1028X) (Chui_2014). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Color Diagnostics, LLC DBA Color Health	RCV000572401	SCV000908421	likely benign	Hereditary cancer-predisposing syndrome	2018-03-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996068	SCV004835072	likely benign	Lynch syndrome	2023-03-28	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000587235	SCV001554267	uncertain significance	not provided		no assertion criteria provided	clinical testing