ClinVar Miner

Submissions for variant NM_015450.3(POT1):c.1532C>T (p.Ser511Phe)

dbSNP: rs1554416456
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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 RCV000564958 SCV000674423 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-19 criteria provided, single submitter clinical testing The p.S511F variant (also known as c.1532C>T), located in coding exon 12 of the POT1 gene, results from a C to T substitution at nucleotide position 1532. The serine at codon 511 is replaced by phenylalanine, an amino acid with highly dissimilar 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV002304215 SCV002594201 uncertain significance Tumor predisposition syndrome 3 2024-12-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 511 of the POT1 protein (p.Ser511Phe). This variant is not present in population databases (gnomAD no frequency). 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: 486152). 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%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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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