ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.379A>C (p.Arg127=)

dbSNP: rs587779007
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562948 SCV000662093 likely benign Hereditary cancer-predisposing syndrome 2021-11-29 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000610025 SCV000712635 uncertain significance not specified 2016-11-17 criteria provided, single submitter clinical testing The p.Arg127Arg variant in MLH1 has been reported in 1 individual with colon can cer by the International Society for Gastrointestinal Hereditary Tumours (InSiGH T) variation database (http://chromium.lovd.nl/LOVD2/colon_cancer), and was abse nt from large population studies. This variant does not change an amino acid but is located in the last three bases of the exon, which is part of the 5? splice region. Computational tools predict a possible impact to splicing. However, this information is not predictive enough to determine pathogenicity. In summary, th e clinical significance of the p.Arg127Arg variant is uncertain.
Invitae RCV000689143 SCV000816783 likely benign Hereditary nonpolyposis colorectal neoplasms 2024-01-19 criteria provided, single submitter clinical testing
GeneDx RCV001549990 SCV001770242 uncertain significance not provided 2023-07-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge

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