ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.2989A>C (p.Ser997Arg)

dbSNP: rs2139550718
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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 RCV002023814 SCV002304490 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2021-10-08 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with arginine at codon 997 of the MLH3 protein (p.Ser997Arg). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and arginine. This variant has not been reported in the literature in individuals affected with MLH3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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 RCV004046854 SCV002751445 uncertain significance not specified 2024-09-08 criteria provided, single submitter clinical testing The p.S997R variant (also known as c.2989A>C), located in coding exon 1 of the MLH3 gene, results from an A to C substitution at nucleotide position 2989. The serine at codon 997 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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