Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001031652 | SCV001194958 | pathogenic | Carney complex, type 1 | 2019-10-17 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 3-11 of the PRKAR1A gene. The 5' boundary is likely confined to intron 2. 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. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. A similar deletion of exons 3-11 has been observed to be de novo in an individual affected with Carney complex (PMID: 21850686). This variant disrupts the hinge domain and two cyclic AMP binding domains of the PRKAR1A protein, which encodes the R1-alpha regulatory subunit of cyclic AMP-dependent protein kinase (PMID: 15992699). While functional studies have not been performed to directly test the effect of this variant on PRKAR1A protein function, this suggests that disruption of this region of the protein is causative of disease. For these reasons, this variant has been classified as Pathogenic. |