ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.352A>G (p.Thr118Ala)

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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 RCV003338959 SCV004058305 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-17 criteria provided, single submitter clinical testing The p.T118A variant (also known as c.352A>G), located in coding exon 4 of the POT1 gene, results from an A to G substitution at nucleotide position 352. The threonine at codon 118 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003585384 SCV004336372 uncertain significance Tumor predisposition syndrome 3 2023-06-05 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 118 of the POT1 protein (p.Thr118Ala). 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 (no rsID available, gnomAD 0.004%).
GeneDx RCV004593267 SCV005078542 uncertain significance not provided 2023-10-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28393830)

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