Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000695382 | SCV000823878 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2020-12-02 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 histidine with tyrosine at codon 479 of the PMS2 protein (p.His479Tyr). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and tyrosine. |
| Ambry Genetics | RCV001011562 | SCV001171898 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-12-14 | criteria provided, single submitter | clinical testing | The p.H479Y variant (also known as c.1435C>T), located in coding exon 11 of the PMS2 gene, results from a C to T substitution at nucleotide position 1435. The histidine at codon 479 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. |