ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.716T>G (p.Ile239Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004055316 SCV002667107 uncertain significance not specified 2022-09-22 criteria provided, single submitter clinical testing The p.I239S variant (also known as c.716T>G), located in coding exon 1 of the MLH3 gene, results from a T to G substitution at nucleotide position 716. The isoleucine at codon 239 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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 RCV003614130 SCV004549893 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2023-12-26 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 239 of the MLH3 protein (p.Ile239Ser). This variant is present in population databases (rs777040433, gnomAD 0.03%). 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: 1757480). 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.

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