Submissions for variant NM_000249.4(MLH1):c.516A>G (p.Glu172=)

dbSNP: rs748128054

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000573935	SCV000662115	likely benign	Hereditary cancer-predisposing syndrome	2017-08-01	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	RCV000629752	SCV000750708	likely benign	Hereditary nonpolyposis colorectal neoplasms	2023-11-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000829149	SCV000970862	likely benign	not provided	2021-03-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000573935	SCV001339628	likely benign	Hereditary cancer-predisposing syndrome	2018-11-26	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003150277	SCV003838205	likely benign	Breast and/or ovarian cancer	2022-02-15	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000829149	SCV004220890	uncertain significance	not provided	2022-09-30	criteria provided, single submitter	clinical testing	To the best of our knowledge, the variant has not been reported in individuals with MLH1-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251454 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on splicing yielded predictions that this variant does not affect MLH1 mRNA splicing . Based on the available information, we are unable to determine the clinical significance of this variant.
PreventionGenetics, part of Exact Sciences	RCV003900248	SCV004711291	likely benign	MLH1-related disorder	2023-03-21	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).