Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000549161 | SCV000655172 | uncertain significance | Tumor predisposition syndrome 3 | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 69 of the POT1 protein (p.Leu69Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with osteosarcoma (PMID: 32191290). ClinVar contains an entry for this variant (Variation ID: 475070). 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. |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV003225731 | SCV003807273 | uncertain significance | Glioma susceptibility 9 | 2022-03-03 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 |
Ambry Genetics | RCV003159929 | SCV003854463 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-27 | criteria provided, single submitter | clinical testing | The p.L69F variant (also known as c.205C>T), located in coding exon 3 of the POT1 gene, results from a C to T substitution at nucleotide position 205. The leucine at codon 69 is replaced by phenylalanine, an amino acid with highly 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. |