Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000630023 | SCV000750979 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2017-12-28 | 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with PMS2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with isoleucine at codon 222 of the PMS2 protein (p.Ser222Ile). The serine residue is weakly conserved and there is a large physicochemical difference between serine and isoleucine. |
Ambry Genetics | RCV002360498 | SCV002663845 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-05-07 | criteria provided, single submitter | clinical testing | The p.S222I variant (also known as c.665G>T), located in coding exon 6 of the PMS2 gene, results from a G to T substitution at nucleotide position 665. The serine at codon 222 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is not 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. |