ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.2768T>G (p.Phe923Cys)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV004064169 SCV002747181 uncertain significance not specified 2023-09-21 criteria provided, single submitter clinical testing The p.F923C variant (also known as c.2768T>G), located in coding exon 1 of the MLH3 gene, results from a T to G substitution at nucleotide position 2768. The phenylalanine at codon 923 is replaced by cysteine, an amino acid with highly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003102194 SCV003454600 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2022-10-19 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 923 of the MLH3 protein (p.Phe923Cys). This variant is present in population databases (rs768629222, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. 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.
Fulgent Genetics, Fulgent Genetics RCV005008586 SCV005635777 uncertain significance Endometrial carcinoma; Colorectal cancer, hereditary nonpolyposis, type 7; Colorectal cancer 2024-04-30 criteria provided, single submitter clinical testing

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