Submissions for variant NM_000179.3(MSH6):c.1665A>G (p.Ala555=)

gnomAD frequency: 0.00066  dbSNP: rs146785465

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212650	SCV000170354	benign	not specified	2014-02-18	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.
Ambry Genetics	RCV000126827	SCV000213112	likely benign	Hereditary cancer-predisposing syndrome	2019-05-21	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.
Invitae	RCV001084346	SCV000252624	benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000662603	SCV000430962	uncertain significance	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, 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.
Genetic Services Laboratory, University of Chicago	RCV000212650	SCV000595847	likely benign	not specified	2017-04-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000126827	SCV000685210	likely benign	Hereditary cancer-predisposing syndrome	2015-05-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586048	SCV000695792	benign	not provided	2016-01-05	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000212650	SCV000706962	likely benign	not specified	2017-04-28	criteria provided, single submitter	clinical testing
Counsyl	RCV000662603	SCV000785240	likely benign	Lynch syndrome 5	2017-06-10	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212650	SCV000888246	benign	not specified	2021-07-21	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000212650	SCV001160622	likely benign	not specified	2019-06-21	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000126827	SCV002535646	likely benign	Hereditary cancer-predisposing syndrome	2021-06-14	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000662603	SCV004018987	benign	Lynch syndrome 5	2023-03-29	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.
CeGaT Center for Human Genetics Tuebingen	RCV000586048	SCV004033731	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	MSH6: BP4, BP7
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003492571	SCV004239300	likely benign	Breast and/or ovarian cancer	2023-01-26	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003997443	SCV004837682	likely benign	Lynch syndrome	2024-01-08	criteria provided, single submitter	clinical testing