Submissions for variant NM_000249.4(MLH1):c.2040C>T (p.Cys680=)

dbSNP: rs63749867

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001711130	SCV000513633	likely benign	not provided	2019-08-29	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 11879922, 22608206)
Invitae	RCV000541158	SCV000625118	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-30	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000567661	SCV000662031	likely benign	Hereditary cancer-predisposing syndrome	2015-05-20	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.
Counsyl	RCV000662499	SCV000785021	likely benign	Colorectal cancer, hereditary nonpolyposis, type 2	2017-03-23	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV000075494	SCV000887331	uncertain significance	Lynch syndrome	2018-05-01	criteria provided, single submitter	clinical testing	MLH1 NM_000249.3:c.2040C>T has a 20.4% probability of pathogenicity based on combining prior probability from public data with likelihood ratios of 0.16 and 1.56 to 1, generated from evidence of seeing this as a somatic mutation in independent tumors with and without loss of heterozygosity at the MLH1 locus. See Shirts et al 2018, PMID 29887214.
Color Diagnostics, LLC DBA Color Health	RCV000567661	SCV000911179	likely benign	Hereditary cancer-predisposing syndrome	2017-09-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000567661	SCV002528706	likely benign	Hereditary cancer-predisposing syndrome	2022-03-05	criteria provided, single submitter	curation
Myriad Genetics, Inc.	RCV000662499	SCV004018179	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.