Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000479971 | SCV000567505 | uncertain significance | not provided | 2020-03-26 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); While protein-based in silico analysis supports that this variant does not alter protein structure/function, splice predictors support a deleterious effect.; Has not been previously published as pathogenic or benign to our knowledge |
Invitae | RCV000794983 | SCV000934421 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2021-10-13 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. ClinVar contains an entry for this variant (Variation ID: 419598). 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 asparagine with lysine at codon 371 of the PMS2 protein (p.Asn371Lys). The asparagine residue is weakly conserved and there is a moderate physicochemical difference between asparagine and lysine. |
Ambry Genetics | RCV001017366 | SCV001178440 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-21 | criteria provided, single submitter | clinical testing | The p.N371K variant (also known as c.1113T>G), located in coding exon 10 of the PMS2 gene, results from a T to G substitution at nucleotide position 1113. The asparagine at codon 371 is replaced by lysine, an amino acid with 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. |