ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.481T>C (p.Cys161Arg)

gnomAD frequency: 0.00001  dbSNP: rs368724856
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000655383 SCV000777313 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2019-07-26 criteria provided, single submitter clinical testing 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MLH3-related disease. This variant is present in population databases (rs368724856, ExAC 0.001%). This sequence change replaces cysteine with arginine at codon 161 of the MLH3 protein (p.Cys161Arg). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and arginine.
Ambry Genetics RCV004025959 SCV003913797 uncertain significance not specified 2023-02-19 criteria provided, single submitter clinical testing The p.C161R variant (also known as c.481T>C), located in coding exon 1 of the MLH3 gene, results from a T to C substitution at nucleotide position 481. The cysteine at codon 161 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005004316 SCV005633326 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-04-12 criteria provided, single submitter clinical testing

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