Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000707760 | SCV000836870 | pathogenic | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 | 2018-04-13 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 3-4 of the SDHD 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. Deletion of exons 3-4 has been reported in individuals affected with head and neck paragangliomas (PMID: 19351833). Deletions of exon 4 have been reported in individuals and families affected with paragangliomas and have been determined to be pathogenic (PMID: 19454582, 20111059, 22382802, 11897817, 25720320, Invitae). This suggests that this region is critical for SDHD protein function and deletions that fully encompass this region may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. |