ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.1141C>T (p.His381Tyr) (rs63750557)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000627703 SCV000543571 uncertain significance Hereditary nonpolyposis colon cancer 2018-01-04 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 381 of the MLH1 protein (p.His381Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. The frequency data for this variant (rs63750557) in the population databases is unreliable, as metrics indicate poor quality at this position in the ExAC database. This variant has been reported in an individual affected with gastric cancer (PMID: 16237216). ClinVar contains an entry for this variant (Variation ID: 89649). Experimental studies have shown that this missense change does not impact MLH1 stability or its ability to interact with PMS2 (PMID: 22252508). 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 RCV000562688 SCV000673847 uncertain significance Hereditary cancer-predisposing syndrome 2017-05-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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