ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1814A>C (p.Glu605Ala)

dbSNP: rs2085305097
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001220166 SCV001392142 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-03-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 605 of the MLH1 protein (p.Glu605Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with a clinical suspicion of Lynch syndrome (PMID: 25437057). ClinVar contains an entry for this variant (Variation ID: 948831). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MLH1 protein function. Experimental studies have shown that this missense change does not substantially affect MLH1 function (PMID: 27629256). 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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