Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001385635 | SCV001585550 | pathogenic | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2020-10-26 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 2-8 of the SDHB 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. 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. Deletion of exons 2-8 has not been reported in the literature in individuals with an SDHB-related disease. Smaller exonic deletions within exons 2-8 have been reported in individuals affected with paraganglioma and/or pheochromocytoma (PMID: 17652212, 19029228, 22517554, 24977658). Furthermore, several missense substitutions between exons 2-8 have been determined to be pathogenic, including p.Trp200Cys (PMID: 20119652, 22835832), p.Cys196Tyr (PMID: 21172883, 19064958), and p.Val140Phe (PMID: 20583550, 20503330). This suggests that this region is critical for SDHB protein function. For these reasons, this variant has been classified as Pathogenic. |