Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000560931 | SCV000663583 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-10-26 | criteria provided, single submitter | clinical testing | The c.160_162delGTA variant (also known as p.V54del) is located in coding exon 2 of the PTEN gene. This variant results from an in-frame GTA deletion at nucleotide positions 160 to 162. This results in the deletion of a valine residue at codon 54. This alteration was reported in an individual with a personal history of endometrial as well breast cancer and she had a Cleveland Clinic score of 66 indicating Cowden syndrome (Ngeow J et al. J. Clin. Oncol., 2014 Jun;32:1818-24). Based on internal structural analysis, p.V54del is predicted to significantly disrupt the structure of the PTEN protein, which may result in a change or loss of function (Paukstelis PJ et al. Mol. Cell, 2005 Feb;17:417-28; Dunham TD et al. EMBO J., 2009 Jun;28:1792-802; Lee JO et al. Cell, 1999 Oct;99:323-34). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD) (Lek M et al. Nature, 2016 08;536:285-91). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by PROVEAN in silico analysis (Choi Y et al., Bioinformatics 2015 Aug; 31(16):2745-7). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |