Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000213152 | SCV000275845 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-28 | criteria provided, single submitter | clinical testing | The p.G105D variant (also known as c.314G>A), located in coding exon 4 of the PMS2 gene, results from a G to A substitution at nucleotide position 314. The glycine at codon 105 is replaced by aspartic acid, an amino acid with similar properties. This variant has been reported in a 73 year old individual with MSI-H colorectal cancer; however, MLH1 and PMS2 proteins were present on immunohistochemistry. The family history consisted of one relative with stomach cancer diagnosed at age 75 and one relative with endometrial cancer diagnosed at age 80 (Wang Q et al. J Med Genet, 2020 07;57:487-499). The amino acid position is highly 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. |
| Color Diagnostics, |
RCV000213152 | SCV000686189 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000629739 | SCV000750695 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-05-19 | 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. 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 expected to disrupt PMS2 protein function. ClinVar contains an entry for this variant (Variation ID: 231866). This missense change has been observed in individual(s) with clinical features of Lynch syndrome (PMID: 31992580). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 105 of the PMS2 protein (p.Gly105Asp). |