Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002230437 | SCV000552027 | uncertain significance | Hereditary nonpolyposis colorectal neoplasms | 2022-01-29 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases (gnomAD) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. 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 disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 411064). This variant has not been reported in the literature in individuals affected with PMS2-related conditions. This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 816 of the PMS2 protein (p.Val816Glu). |
Ambry Genetics | RCV003168842 | SCV003883823 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-11-10 | criteria provided, single submitter | clinical testing | The p.V816E variant (also known as c.2447T>A), located in coding exon 15 of the PMS2 gene, results from a T to A substitution at nucleotide position 2447. The valine at codon 816 is replaced by glutamic acid, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |