ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.338T>A (p.Val113Asp) (rs63750559)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164616 SCV000215280 uncertain significance Hereditary cancer-predisposing syndrome 2014-06-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Invitae RCV000547399 SCV000625150 uncertain significance Hereditary nonpolyposis colon cancer 2017-07-18 criteria provided, single submitter clinical testing This sequence change replaces valine with aspartic acid at codon 113 of the MLH1 protein (p.Val113Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with Lynch syndrome in the literature (PMID: 16395668) and in the Universal Mutation Database (PMID: 10612827). ClinVar contains an entry for this variant (Variation ID: 90172). Algorithms developed specifically for the MLH1 gene (PMID: 22290698, 18383312) suggest that this missense change is likely to be deleterious. However, these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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