ClinVar Miner

Submissions for variant NM_000249.3(MLH1):c.242C>T (p.Thr81Ile) (rs63751069)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122976 SCV000166252 uncertain significance Hereditary nonpolyposis colon cancer 2018-09-27 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 81 of the MLH1 protein (p.Thr81Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs63751069, ExAC 0.02%). This variant has not been reported as a germline variant in the literature in individuals with MLH1-related disease. ClinVar contains an entry for this variant (Variation ID: 135852). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT and Align-GVGD) both 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.
Ambry Genetics RCV000567161 SCV000676051 uncertain significance Hereditary cancer-predisposing syndrome 2016-09-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence

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