Submissions for variant NM_000179.3(MSH6):c.116G>A (p.Gly39Glu)

gnomAD frequency: 0.18742  dbSNP: rs1042821

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
International Society for Gastrointestinal Hereditary Tumours (InSiGHT)	RCV000030258	SCV000107840	no known pathogenicity	Lynch syndrome	2013-09-05	reviewed by expert panel	research	MAF >1%
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000035318	SCV000058966	benign	not specified	2008-10-29	criteria provided, single submitter	clinical testing	Gly39Glu in exon 1 of MSH6: This variant is not expected to have clinical signif icance because it has been identified in 17% (1336/7748) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS/rs1042821). Gly39Glu in exon 1 of MSH6 (rs1042821; a llele frequency = 17%, 1336/7748) **
Eurofins Ntd Llc (ga)	RCV000035318	SCV000110149	benign	not specified	2016-02-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000132091	SCV000187155	benign	Hereditary cancer-predisposing syndrome	2014-10-27	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.
Color Diagnostics, LLC DBA Color Health	RCV000132091	SCV000292086	benign	Hereditary cancer-predisposing syndrome	2014-11-04	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000035318	SCV000302867	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000609254	SCV000430945	likely benign	Lynch syndrome 5	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000034489	SCV000604270	benign	not provided	2023-11-30	criteria provided, single submitter	clinical testing
IntelligeneCG	RCV000144626	SCV000611715	benign	Lynch syndrome 1	2017-08-18	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079921	SCV000624619	benign	Hereditary nonpolyposis colorectal neoplasms	2025-02-04	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000609254	SCV000744284	benign	Lynch syndrome 5	2015-09-21	criteria provided, single submitter	clinical testing
Mendelics	RCV000609254	SCV001135774	benign	Lynch syndrome 5	2019-05-28	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262327	SCV001440150	benign	Breast carcinoma	2019-01-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000034489	SCV001892538	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24622885, 29442465, 28932927, 27153395, 18523027, 19582761, 24689082, 22949387, 19685280, 22703879)
Sema4, Sema4	RCV000132091	SCV002535607	benign	Hereditary cancer-predisposing syndrome	2019-12-11	criteria provided, single submitter	curation
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000609254	SCV004015980	benign	Lynch syndrome 5	2023-07-07	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000030258	SCV004827941	benign	Lynch syndrome	2024-10-03	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000034489	SCV005243543	benign	not provided		criteria provided, single submitter	not provided
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV000609254	SCV005442081	benign	Lynch syndrome 5	2024-12-19	criteria provided, single submitter	clinical testing
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000034489	SCV000043349	no known pathogenicity	not provided	2012-07-13	no assertion criteria provided	research	Converted during submission to Benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000030258	SCV000052925	benign	Lynch syndrome	2011-12-02	no assertion criteria provided	clinical testing
Pathway Genomics	RCV000144626	SCV000189953	benign	Lynch syndrome 1	2014-07-24	no assertion criteria provided	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000035318	SCV000257208	benign	not specified		no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001353505	SCV000592563	benign	Carcinoma of colon		no assertion criteria provided	clinical testing	The p.Gly39Glu variant has been previously reported in the literature and is recorded in dbSNP as a polymorphism with an average heterozygosity of 0.307+/-0.243 (dbSNP#: rs1042821); this appreciable frequency in different populations of origin increases the likelihood this is a benign variant. In addition, this variant has been identified by our laboratory in at least one individual with a second pathogenic vairiant, increasing the likelihood this variant is benign. In summary, based on the above information, this variant is classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000609254	SCV000734206	benign	Lynch syndrome 5		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000035318	SCV001906443	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000035318	SCV001921533	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000035318	SCV001959944	benign	not specified		no assertion criteria provided	clinical testing