Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001754747 | SCV001996341 | uncertain significance | not provided | 2019-09-25 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes splice predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002388646 | SCV002707317 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-02 | criteria provided, single submitter | clinical testing | The c.150G>A variant (also known as p.V50V), located in coding exon 3 of the POT1 gene, results from a G to A substitution at nucleotide position 150. This nucleotide substitution does not change the valine at codon 50. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Based on the available evidence, the clinical significance of this variant remains unclear. |
Labcorp Genetics |
RCV002540352 | SCV002983749 | uncertain significance | Tumor predisposition syndrome 3 | 2024-08-03 | criteria provided, single submitter | clinical testing | This sequence change affects codon 50 of the POT1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the POT1 protein. 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: 1308859). 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. |