Submissions for variant NM_000249.4(MLH1):c.1266C>T (p.Gly422=)

dbSNP: rs63750791

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000218731	SCV000274501	likely benign	Hereditary cancer-predisposing syndrome	2015-03-15	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000524230	SCV000284014	benign	Hereditary nonpolyposis colorectal neoplasms	2024-02-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001355583	SCV000530730	likely benign	not provided	2021-05-18	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 15996210, 18726168)
Color Diagnostics, LLC DBA Color Health	RCV000218731	SCV000689798	benign	Hereditary cancer-predisposing syndrome	2017-02-21	criteria provided, single submitter	clinical testing
Counsyl	RCV000662538	SCV000785115	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2017-04-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000662538	SCV001308771	uncertain significance	Colorectal cancer, hereditary nonpolyposis, type 2	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Genetic Services Laboratory, University of Chicago	RCV001818238	SCV002071355	likely benign	not specified	2019-11-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000218731	SCV002528634	benign	Hereditary cancer-predisposing syndrome	2021-02-13	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000662538	SCV004018182	benign	Colorectal cancer, hereditary nonpolyposis, type 2	2023-03-15	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001355583	SCV004220062	likely benign	not provided	2022-11-29	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003997107	SCV004840984	benign	Lynch syndrome	2024-01-11	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355583	SCV001550508	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004748552	SCV005349582	likely benign	MLH1-related disorder	2019-06-30	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).