Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000811969 | SCV000952266 | uncertain significance | Tumor predisposition syndrome 3 | 2022-12-03 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 655723). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 317 of the POT1 protein (p.Ser317Gly). |
Ambry Genetics | RCV001019407 | SCV001180762 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-14 | criteria provided, single submitter | clinical testing | The c.949A>G variant (also known as p.S317G), located in coding exon 7 of the POT1 gene, results from an A to G substitution at nucleotide position 949. The amino acid change results in serine to glycine at codon 317, an amino acid with similar properties. However, this change occurs in the last base pair of coding exon 7, which makes it likely to have some effect on normal mRNA splicing. This amino acid position is well 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. |