Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000239810 | SCV000299124 | pathogenic | Peutz-Jeghers syndrome | 2016-01-27 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 1 of the STK11 gene, which includes the initiator codon. It is predicted to result in an absent or truncated protein product. The 5' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. The 3' boundary is likely confined to intron 1 of the STK11 gene. Truncating variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). Similar deletions of exon 1 have been reported in Peutz-Jeghers syndrome patients (PMID: 22382802, 19727776, 24260271) and in a patient with gastrointestinal polyposis (PMID: 23399955). Exonic deletions are a common cause of Peutz-Jeghers syndrome; in cohort studies it has been shown that deletions account for ~16% to 30% of reported cases (PMID: 20623358, 16287113). Exon 1 of STK11 contains the translation initiator codon and a portion of the protein kinase domain, as well as several residues predicted to be phosphorylated which are needed for protein localization (PMID: 12829253), suggesting that this deletion is likely to abrogate production of the STK11 protein. For these reasons, this variant has been classified as Pathogenic. |