Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000602694 | SCV000731827 | likely pathogenic | PTEN hamartoma tumor syndrome | 2018-02-05 | criteria provided, single submitter | clinical testing | The p.Tyr174X variant in PTEN has not been previously reported in individuals wi th PTEN-associated phenotypes or in large population studies. This nonsense vari ant leads to a premature termination codon at position 174, which is predicted t o lead to a truncated or absent protein. Heterozygous loss of function of the PT EN gene is an established disease mechanism in individuals with PTEN hamartoma t umor syndrome. In summary, although additional studies are required to fully est ablish its clinical significance, the p.Tyr174X variant is likely pathogenic. ACMG/AMP criteria applied: PVS1, PM2 (Richards 2015). |
| Ambry Genetics | RCV002343167 | SCV002646766 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-10-05 | criteria provided, single submitter | clinical testing | The p.Y174* pathogenic mutation (also known as c.522T>G), located in coding exon 6 of the PTEN gene, results from a T to G substitution at nucleotide position 522. This changes the amino acid from a tyrosine to a stop codon within coding exon 6. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV000602694 | SCV004641604 | pathogenic | PTEN hamartoma tumor syndrome | 2023-07-18 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 517520). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr174*) in the PTEN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). For these reasons, this variant has been classified as Pathogenic. |