Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV003278424 | SCV004009209 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-05-26 | criteria provided, single submitter | clinical testing | The c.696dupA pathogenic mutation, located in coding exon 7 of the PTEN gene, results from a duplication of A at nucleotide position 696, causing a translational frameshift with a predicted alternate stop codon (p.R233Tfs*10). In a study of 3,515 research participants who met at least the relaxed International Cowden Consortium operational criteria for Cowden syndrome, this alteration was identified in a patient with two diagnoses of breast cancer (Ngeow J et al. J Clin Oncol, 2014 Jun;32:1818-24). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, 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. |