ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.799G>A (p.Val267Ile)

gnomAD frequency: 0.00001  dbSNP: rs876660752
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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 RCV000216379 SCV000278422 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-08 criteria provided, single submitter clinical testing The p.V267I variant (also known as c.799G>A), located in coding exon 10 of the MLH1 gene, results from a G to A substitution at nucleotide position 799. The valine at codon 267 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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.
Invitae RCV001050572 SCV001214687 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2023-05-25 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MLH1-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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MLH1 protein function. ClinVar contains an entry for this variant (Variation ID: 233949). This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 267 of the MLH1 protein (p.Val267Ile).
All of Us Research Program, National Institutes of Health RCV003998589 SCV004822005 uncertain significance Lynch syndrome 2023-06-27 criteria provided, single submitter clinical testing

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