Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000545956 | SCV000625536 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2017-05-09 | criteria provided, single submitter | clinical testing | In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a PMS2-related disease. This sequence change replaces histidine with asparagine at codon 514 of the PMS2 protein (p.His514Asn). The histidine residue is weakly conserved and there is a small physicochemical difference between histidine and asparagine. |
| Color Diagnostics, |
RCV000582193 | SCV000691026 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000582193 | SCV002705063 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-04-01 | criteria provided, single submitter | clinical testing | The p.H514N variant (also known as c.1540C>A), located in coding exon 11 of the PMS2 gene, results from a C to A substitution at nucleotide position 1540. The histidine at codon 514 is replaced by asparagine, an amino acid with similar properties. This amino acid position is poorly 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. |