Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000555287 | SCV000655118 | uncertain significance | Tumor predisposition syndrome 3 | 2021-03-14 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a POT1-related disease. This sequence change replaces tyrosine with histidine at codon 360 of the POT1 protein (p.Tyr360His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. |
| Ambry Genetics | RCV001009865 | SCV001169987 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-03 | criteria provided, single submitter | clinical testing | The p.Y360H variant (also known as c.1078T>C), located in coding exon 9 of the POT1 gene, results from a T to C substitution at nucleotide position 1078. The tyrosine at codon 360 is replaced by histidine, an amino acid with 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. |