ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1183G>A (p.Gly395Ser)

gnomAD frequency: 0.00002  dbSNP: rs757373061
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000652214 SCV000774082 uncertain significance Tumor predisposition syndrome 3 2023-12-16 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 395 of the POT1 protein (p.Gly395Ser). This variant is present in population databases (rs757373061, gnomAD 0.003%). This missense change has been observed in individual(s) with brain oligodendroglioma (PMID: 34193977). ClinVar contains an entry for this variant (Variation ID: 541870). 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.
Ambry Genetics RCV001010080 SCV001170228 uncertain significance Hereditary cancer-predisposing syndrome 2021-06-03 criteria provided, single submitter clinical testing The p.G395S variant (also known as c.1183G>A), located in coding exon 10 of the POT1 gene, results from a G to A substitution at nucleotide position 1183. The glycine at codon 395 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV003237976 SCV002011637 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV002268237 SCV002550098 uncertain significance not specified 2023-08-15 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002493048 SCV002779402 uncertain significance Tumor predisposition syndrome 3; Glioma susceptibility 9 2022-05-24 criteria provided, single submitter clinical testing

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