Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001032176 | SCV001195483 | pathogenic | Peutz-Jeghers syndrome | 2019-01-04 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-9 of the STK11 gene. The 5' boundary is likely confined to intron 1. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. Exon 10 of STK11 is non-coding and is not included in the assayed region. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product by eliminating more than 300 amino acid residues (>70%) from the full length protein or disrupt mRNA translation. This variant has not been reported in the literature in individuals with STK11-related disease. However a similar deletion encompassing exons 2-10 (PMID: 16287113) has been reported in individuals affected with Peutz Jeghers syndrome (PJS). This deletion removes the majority of the protein kinase domain of the STK11 protein. Loss of STK11 kinase activity has been reported to cause PJS (PMID: 9837816, 15987703). Sub-genic deletion of exons 3-9 has been determined to be pathogenic (PMID: 24652667, 26386697, Invitae). Therefore, deletions that fully encompass that region are also expected to be pathogenic. For these reasons, this variant has been classified as Pathogenic. |