Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000572151 | SCV000670867 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-09-19 | criteria provided, single submitter | clinical testing | The p.I227V variant (also known as c.679A>G), located in coding exon 6 of the PMS2 gene, results from an A to G substitution at nucleotide position 679. The isoleucine at codon 227 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly 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. |
Invitae | RCV001858332 | SCV002256618 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-09-25 | criteria provided, single submitter | clinical testing | Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PMS2 protein function. 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. ClinVar contains an entry for this variant (Variation ID: 484329). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with valine at codon 227 of the PMS2 protein (p.Ile227Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. |