ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3785C>T (p.Pro1262Leu)

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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 RCV004048082 SCV002622566 uncertain significance not specified 2023-04-01 criteria provided, single submitter clinical testing The p.P1262L variant (also known as c.3785C>T), located in coding exon 7 of the MLH3 gene, results from a C to T substitution at nucleotide position 3785. The proline at codon 1262 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003094366 SCV003469721 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-12-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1262 of the MLH3 protein (p.Pro1262Leu). This variant is present in population databases (rs377662571, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1734874). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV005008541 SCV005635754 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-01-17 criteria provided, single submitter clinical testing

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