ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1431A>T (p.Arg477Ser)

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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 RCV003747283 SCV004433391 uncertain significance Tumor predisposition syndrome 3 2023-05-08 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 POT1 protein function. This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is present in population databases (rs751455733, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 477 of the POT1 protein (p.Arg477Ser).
Ambry Genetics RCV004654285 SCV005150663 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-08 criteria provided, single submitter clinical testing The p.R477S variant (also known as c.1431A>T), located in coding exon 11 of the POT1 gene, results from an A to T substitution at nucleotide position 1431. The arginine at codon 477 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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