ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1487C>T (p.Pro496Leu) (rs63750226)

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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 RCV000164380 SCV000215015 uncertain significance Hereditary cancer-predisposing syndrome 2017-08-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000455152 SCV000539648 uncertain significance not specified 2016-06-23 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported as somatic mutation in 1 tumor, 1 functional study show 65% MMR activity; ClinVar: 1 VUS
Invitae RCV000473679 SCV000543555 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-25 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 496 of the MLH1 protein (p.Pro496Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (rs63750226, ExAC no frequency). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 185027). An experimental study has shown that this missense change does not affect MLH1 protein function in vitro or in a yeast-based assay (PMID: 17510385). 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.
Counsyl RCV000662426 SCV000784877 uncertain significance Lynch syndrome II 2017-01-25 criteria provided, single submitter clinical testing

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