ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.1856A>T (p.Lys619Ile)

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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 RCV004326169 SCV003999113 uncertain significance not specified 2023-05-25 criteria provided, single submitter clinical testing The p.K619I variant (also known as c.1856A>T), located in coding exon 1 of the MLH3 gene, results from an A to T substitution at nucleotide position 1856. The lysine at codon 619 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003505322 SCV004299830 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-03-06 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 619 of the MLH3 protein (p.Lys619Ile). This variant is present in population databases (rs751984694, gnomAD 0.003%). 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: 2561653). 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 RCV005012860 SCV005635789 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-01-18 criteria provided, single submitter clinical testing

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