ClinVar Miner

Submissions for variant NM_000249.4(MLH1):c.1768T>G (p.Leu590Val)

dbSNP: rs927866628
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001037924 SCV001201361 uncertain significance Hereditary nonpolyposis colorectal neoplasms 2022-03-26 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. 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: 836731). This variant has not been reported in the literature in individuals affected with MLH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 590 of the MLH1 protein (p.Leu590Val).
Ambry Genetics RCV002400225 SCV002710645 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-31 criteria provided, single submitter clinical testing The p.L590V variant (also known as c.1768T>G), located in coding exon 16 of the MLH1 gene, results from a T to G substitution at nucleotide position 1768. The leucine at codon 590 is replaced by valine, an amino acid with highly similar 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.

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