Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164657 | SCV000215322 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-30 | criteria provided, single submitter | clinical testing | The p.H435Y variant (also known as c.1303C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1303. The histidine at codon 435 is replaced by tyrosine, 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. |
| Invitae | RCV000168171 | SCV000218833 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 435 of the PMS2 protein (p.His435Tyr). This variant is present in population databases (rs148956636, gnomAD 0.0009%). This missense change has been observed in individual(s) with pancreatic cancer (PMID: 35171259). ClinVar contains an entry for this variant (Variation ID: 185267). 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 with a negative predictive value of 80%. 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. |
| Color Diagnostics, |
RCV000164657 | SCV000909656 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-26 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001582647 | SCV001812570 | uncertain significance | not provided | 2023-04-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with colorectal cancer (Xu et al., 2020); This variant is associated with the following publications: (PMID: 32973888) |
| Baylor Genetics | RCV003467302 | SCV004205485 | uncertain significance | Lynch syndrome 4 | 2023-08-12 | criteria provided, single submitter | clinical testing |