Submissions for variant NM_000249.4(MLH1):c.1020C>G (p.Ser340=)

gnomAD frequency: 0.00005  dbSNP: rs374770981

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163794	SCV000214375	likely benign	Hereditary cancer-predisposing syndrome	2014-11-19	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	RCV001081543	SCV000259845	likely benign	Hereditary nonpolyposis colorectal neoplasms	2024-01-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000424077	SCV000513618	benign	not specified	2015-09-08	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.
Color Diagnostics, LLC DBA Color Health	RCV000163794	SCV000684709	likely benign	Hereditary cancer-predisposing syndrome	2016-06-27	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000205904	SCV001134283	likely benign	not provided	2018-09-11	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000163794	SCV002536425	likely benign	Hereditary cancer-predisposing syndrome	2021-12-05	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003937496	SCV004766220	likely benign	MLH1-related disorder	2019-12-23	criteria provided, single submitter	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).