Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000562349 | SCV000671701 | pathogenic | Hereditary cancer-predisposing syndrome | 2016-07-05 | criteria provided, single submitter | clinical testing | The c.1116_1119delTGAA pathogenic mutation, located in coding exon 9 of the PTEN gene, results from a deletion of 4 nucleotides at nucleotide positions 1116 to 1119, causing a translational frameshift with a predicted alternate stop codon. 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 |
RCV001042817 | SCV001206522 | likely pathogenic | PTEN hamartoma tumor syndrome | 2023-05-01 | criteria provided, single submitter | clinical testing | 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 C-tail domain and PDZ binding domain of the PTEN protein (PMID: 25448482, 25336918, 24905788) and several critical phosphorylation sites within the C-tail domain, which are important for regulating PTEN protein stability and function (PMID: 12297295, 10866658, 11035045, 10468583). While functional studies have not been performed to directly test the effect of this variant on PTEN protein function, this suggests that disruption of this region of the protein is causative of disease. ClinVar contains an entry for this variant (Variation ID: 484597). 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.Glu373Leufs*42) in the PTEN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 31 amino acid(s) of the PTEN protein. |