Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002439466 | SCV002750316 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | The c.275A>T (p.D92V) alteration is located in exon 5 (coding exon 5) of the PTEN gene. This alteration results from an A to T substitution at nucleotide position 275, causing the aspartic acid (D) at amino acid position 92 to be replaced by a valine (V). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Based on internal structural analysis, D92V disrupts the PTEN catalytic pocket at a position with known important in proper catalytic function. Additionally, there are many internally-assessed pathogenic variants within the catalytic pocket, including one at the same position (D92A) (Lee, 1999; Tautz, 2013; Lee, 2015; Tu, 2020). In two functional studies, this variant demonstrated deficient phosphatase activity (Rodríguez-Escudero, 2011; Mighell, 2018). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. |