ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.820A>G (p.Lys274Glu)

gnomAD frequency: 0.00001  dbSNP: rs1892456852
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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 RCV001901547 SCV002173298 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-07-03 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 274 of the MLH3 protein (p.Lys274Glu). This variant is not present in population databases (gnomAD no frequency). 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: 1404235). 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 tolerated. 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 RCV004042613 SCV002679720 uncertain significance not specified 2024-10-31 criteria provided, single submitter clinical testing The p.K274E variant (also known as c.820A>G), located in coding exon 1 of the MLH3 gene, results from an A to G substitution at nucleotide position 820. The lysine at codon 274 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.

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