ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3374A>G (p.Asn1125Ser)

dbSNP: rs2139504673
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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 RCV001917837 SCV002170676 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2024-02-20 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1125 of the MLH3 protein (p.Asn1125Ser). 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: 1399745). 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 RCV004041713 SCV004090268 uncertain significance not specified 2023-09-07 criteria provided, single submitter clinical testing The p.N1125S variant (also known as c.3374A>G), located in coding exon 2 of the MLH3 gene, results from an A to G substitution at nucleotide position 3374. The asparagine at codon 1125 is replaced by serine, an amino acid with highly similar 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.

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