Submissions for variant NM_000251.3(MSH2):c.336C>A (p.Ser112=)

gnomAD frequency: 0.00004  dbSNP: rs34312619

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001082839	SCV000166281	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-19	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000163093	SCV000213599	likely benign	Hereditary cancer-predisposing syndrome	2014-12-01	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.
Illumina Laboratory Services, Illumina	RCV000662370	SCV000430912	uncertain significance	Lynch syndrome 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000420474	SCV000513649	benign	not specified	2015-03-16	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.
Color Diagnostics, LLC DBA Color Health	RCV000163093	SCV000685080	likely benign	Hereditary cancer-predisposing syndrome	2017-02-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000420474	SCV000696261	likely benign	not specified	2019-09-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000662370	SCV000784762	likely benign	Lynch syndrome 1	2017-11-13	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000590813	SCV000889434	likely benign	not provided	2023-06-22	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163093	SCV002534511	likely benign	Hereditary cancer-predisposing syndrome	2021-01-27	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000662370	SCV004018309	benign	Lynch syndrome 1	2023-03-20	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
All of Us Research Program, National Institutes of Health	RCV003997409	SCV004830043	likely benign	Lynch syndrome	2023-12-01	criteria provided, single submitter	clinical testing