ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.379A>C (p.Arg127=) (rs587779007)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562948 SCV000662093 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-15 criteria provided, single submitter clinical testing Insufficient evidence
Laboratory for Molecular Medicine, Partners HealthCare 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 uncertain significance Hereditary nonpolyposis colon cancer 2018-01-18 criteria provided, single submitter clinical testing This sequence change affects codon 127 of the MLH1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MLH1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 90188). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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