ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.365A>G (p.Lys122Arg)

gnomAD frequency: 0.00001  dbSNP: rs762453215
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001064595 SCV001229505 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 122 of the MLH3 protein (p.Lys122Arg). This variant is present in population databases (rs762453215, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. 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: 858670). 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.
Ambry Genetics RCV004030546 SCV002617644 uncertain significance not specified 2022-09-20 criteria provided, single submitter clinical testing The p.K122R variant (also known as c.365A>G), located in coding exon 1 of the MLH3 gene, results from an A to G substitution at nucleotide position 365. The lysine at codon 122 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University RCV003153924 SCV003843645 likely pathogenic Ovarian cancer 2022-01-01 criteria provided, single submitter clinical testing

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