ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1630A>G (p.Met544Val)

gnomAD frequency: 0.00001  dbSNP: rs762424988
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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 RCV000561531 SCV000674405 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-24 criteria provided, single submitter clinical testing The p.M544V variant (also known as c.1630A>G), located in coding exon 13 of the POT1 gene, results from an A to G substitution at nucleotide position 1630. The methionine at codon 544 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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.
Invitae RCV000687246 SCV000814803 uncertain significance Tumor predisposition syndrome 3 2023-12-11 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 544 of the POT1 protein (p.Met544Val). This variant is present in population databases (rs762424988, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with POT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 486136). 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 POT1 protein function with a negative predictive value of 80%. 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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