Submissions for variant NM_000251.3(MSH2):c.2579C>T (p.Ser860Leu)

gnomAD frequency: 0.00001  dbSNP: rs63750849

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000076508	SCV000107537	likely benign	Lynch syndrome	2013-09-05	reviewed by expert panel	research	Multifactorial likelihood analysis posterior probability 0.001-0.049
Labcorp Genetics (formerly Invitae), Labcorp	RCV000524395	SCV000284154	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-11-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001284511	SCV000521068	likely benign	not provided	2021-04-14	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22290698, 22102614, 14871975, 18415027, 18383312, 23417712)
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000438978	SCV000539691	uncertain significance	not specified	2016-10-20	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Classified as LB by InSiGHT expert panel. Another variant at the same position (Ser860X) has been classified as P.
Ambry Genetics	RCV000575134	SCV000662244	likely benign	Hereditary cancer-predisposing syndrome	2023-06-06	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	RCV000575134	SCV000690081	likely benign	Hereditary cancer-predisposing syndrome	2017-09-18	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284511	SCV001470344	uncertain significance	not provided	2020-07-17	criteria provided, single submitter	clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.	RCV000575134	SCV004014887	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-15	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000076508	SCV004826487	likely benign	Lynch syndrome	2024-02-22	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV005246632	SCV005898849	benign	Lynch syndrome 1	2024-12-13	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features consistent with gene-specific recessive disease. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 27363726].
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV005394325	SCV006056463	uncertain significance	Lynch syndrome 1; Muir-Torré syndrome; Mismatch repair cancer syndrome 2	2023-05-31	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004542747	SCV004773025	likely benign	MSH2-related disorder	2023-12-07	no assertion criteria provided	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).