Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000645035 | SCV000766774 | likely pathogenic | PTEN hamartoma tumor syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | This missense change has been observed in individuals with PTEN-related conditions (PMID: 16704655; Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Tyr68 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9467011, 10866302, 19457929, 20926450, 21956414, 24778394, 25669429, 26246517). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects PTEN function (PMID: 21828076). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PTEN protein function. ClinVar contains an entry for this variant (Variation ID: 536540). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 68 of the PTEN protein (p.Tyr68Asp). |