Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002230430 | SCV000551964 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2016-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine with cysteine at codon 320 of the PMS2 protein (p.Phe320Cys). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and cysteine. 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C65"). The cysteine 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. |
| Ambry Genetics | RCV002379476 | SCV002694941 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-21 | criteria provided, single submitter | clinical testing | The p.F320C variant (also known as c.959T>G), located in coding exon 9 of the PMS2 gene, results from a T to G substitution at nucleotide position 959. The phenylalanine at codon 320 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |