ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1744C>G (p.Leu582Val) (rs63751713)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000627697 SCV000543553 uncertain significance Hereditary nonpolyposis colon cancer 2018-12-10 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 582 of the MLH1 protein (p.Leu582Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs63751713, ExAC 0.01%). This variant has been reported in a family affected with hereditary non-polyposis colorectal cancer (HNPCC) (PMID: 7757073). ClinVar contains an entry for this variant (Variation ID: 89869). Experimental studies have shown that this missense change does not adversely affect protein function (PMID: 10037723, 17510385, 15864295, 12810663), although not all of the studies are in agreement (PMID: 9697702). 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.
Ambry Genetics RCV000571505 SCV000662046 uncertain significance Hereditary cancer-predisposing syndrome 2017-12-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000571505 SCV000908644 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-14 criteria provided, single submitter clinical testing

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