Submissions for variant NM_000179.3(MSH6):c.3438+14A>T

gnomAD frequency: 0.32279  dbSNP: rs2020911

Total submissions: 23

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000074853	SCV000108065	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1%
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035324	SCV000058972	benign	not specified	2011-07-22	criteria provided, single submitter	clinical testing	This variant is classified as benign based on its high frequency in the general population (rs2020911, MAF >3%).
Eurofins Ntd Llc (ga)	RCV000035324	SCV000110157	benign	not specified	2015-05-27	criteria provided, single submitter	clinical testing
GeneDx	RCV000035324	SCV000170361	benign	not specified	2014-11-19	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.
PreventionGenetics, part of Exact Sciences	RCV000035324	SCV000302878	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000410944	SCV000430976	benign	Lynch syndrome 5	2018-01-13	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Counsyl	RCV000410944	SCV000487973	benign	Lynch syndrome 5	2015-12-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000448622	SCV000537327	benign	Hereditary cancer-predisposing syndrome	2015-03-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811241	SCV000604273	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000410944	SCV000744299	benign	Lynch syndrome 5	2015-09-21	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001798078	SCV002042050	benign	Breast and/or ovarian cancer	2021-04-22	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002054557	SCV002442274	benign	Hereditary nonpolyposis colorectal neoplasms	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000448622	SCV002615188	benign	Hereditary cancer-predisposing syndrome	2014-08-26	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Fulgent Genetics, Fulgent Genetics	RCV002482955	SCV002802225	benign	Endometrial carcinoma; Lynch syndrome 5; Mismatch repair cancer syndrome 3	2021-08-11	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000410944	SCV004015978	benign	Lynch syndrome 5	2023-07-07	criteria provided, single submitter	clinical testing
Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	RCV000035324	SCV004233052	benign	not specified	2024-01-24	criteria provided, single submitter	clinical testing	This variant is classified as Benign based on local population frequency. This variant was detected in 77% of patients studied by a panel of primary immunodeficiencies. Number of patients: 73. Only high quality variants are reported.
Breakthrough Genomics, Breakthrough Genomics	RCV001811241	SCV005243568	benign	not provided		criteria provided, single submitter	not provided
Mayo Clinic Laboratories, Mayo Clinic	RCV000035324	SCV000257252	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000035324	SCV000592640	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000410944	SCV000734219	benign	Lynch syndrome 5		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000035324	SCV001905842	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035324	SCV001925467	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035324	SCV001953463	benign	not specified		no assertion criteria provided	clinical testing