ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.943C>T (p.His315Tyr) (rs151119913)

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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 RCV000571492 SCV000669556 uncertain significance Hereditary cancer-predisposing syndrome 2016-02-15 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000571492 SCV000689933 uncertain significance Hereditary cancer-predisposing syndrome 2020-03-10 criteria provided, single submitter clinical testing
Invitae RCV001228581 SCV001400986 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2019-09-17 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 315 of the MLH1 protein (p.His315Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs151119913, ExAC 0.003%). This variant has not been reported in the literature in individuals with MLH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 483550). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but 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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