ClinVar Miner

Submissions for variant NM_001040108.2(MLH3):c.3067A>G (p.Ser1023Gly)

gnomAD frequency: 0.00001  dbSNP: rs778414174
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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 RCV000655390 SCV000777320 uncertain significance Colorectal cancer, hereditary nonpolyposis, type 7 2022-04-24 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 544277). This variant has not been reported in the literature in individuals affected with MLH3-related conditions. This variant is present in population databases (rs778414174, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 1023 of the MLH3 protein (p.Ser1023Gly).
Ambry Genetics RCV004025963 SCV002753643 uncertain significance not specified 2023-04-01 criteria provided, single submitter clinical testing The p.S1023G variant (also known as c.3067A>G), located in coding exon 1 of the MLH3 gene, results from an A to G substitution at nucleotide position 3067. The serine at codon 1023 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. 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.

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