Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000813475 | SCV000953836 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2018-12-30 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals with PMS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with aspartic acid at codon 383 of the PMS2 protein (p.Asn383Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid. |
Ambry Genetics | RCV001017463 | SCV001178547 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-09-14 | criteria provided, single submitter | clinical testing | The p.N383D variant (also known as c.1147A>G), located in coding exon 11 of the PMS2 gene, results from an A to G substitution at nucleotide position 1147. The asparagine at codon 383 is replaced by aspartic acid, an amino acid with highly similar 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. |