Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000532949 | SCV000655208 | uncertain significance | Tumor predisposition syndrome 3 | 2023-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 26 of the POT1 protein (p.Tyr26Cys). 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 missense change has been observed in individual(s) with clinical features of POT1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 475102). 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. 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 | RCV002413630 | SCV002673294 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-06 | criteria provided, single submitter | clinical testing | The p.Y26C variant (also known as c.77A>G), located in coding exon 2 of the POT1 gene, results from an A to G substitution at nucleotide position 77. The tyrosine at codon 26 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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. |
Center for Genomic Medicine, |
RCV003493643 | SCV004243335 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing |