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 | 2023-09-21 | 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 variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Labcorp Genetics |
RCV000602694 | SCV004641604 | pathogenic | PTEN hamartoma tumor syndrome | 2023-07-18 | criteria provided, single submitter | clinical testing | 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. ClinVar contains an entry for this variant (Variation ID: 517520). For these reasons, this variant has been classified as Pathogenic. |