ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1682A>G (p.Asp561Gly)

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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 RCV002414545 SCV002715283 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-16 criteria provided, single submitter clinical testing The p.D561G variant (also known as c.1682A>G), located in coding exon 13 of the POT1 gene, results from an A to G substitution at nucleotide position 1682. The aspartic acid at codon 561 is replaced by glycine, an amino acid with 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003097108 SCV003317421 uncertain significance Tumor predisposition syndrome 3 2024-10-09 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 561 of the POT1 protein (p.Asp561Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 1777935). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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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