Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001203470 | SCV001374636 | uncertain significance | Tumor predisposition syndrome 3 | 2022-06-13 | 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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: 934972). 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 aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 286 of the POT1 protein (p.Asp286Asn). |
Ambry Genetics | RCV003293999 | SCV004002066 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-21 | criteria provided, single submitter | clinical testing | The p.D286N variant (also known as c.856G>A), located in coding exon 6 of the POT1 gene, results from a G to A substitution at nucleotide position 856. The aspartic acid at codon 286 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |