ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.1544C>T (p.Pro515Leu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002638309 SCV003520461 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2022-08-30 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 515 of the MLH3 protein (p.Pro515Leu).
Ambry Genetics RCV004072044 SCV005037209 uncertain significance not specified 2024-03-07 criteria provided, single submitter clinical testing The p.P515L variant (also known as c.1544C>T), located in coding exon 1 of the MLH3 gene, results from a C to T substitution at nucleotide position 1544. The proline at codon 515 is replaced by leucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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