Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000546525 | SCV000645370 | pathogenic | Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 | 2017-08-07 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the last exon of the SDHD mRNA at codon 114 (p.Tyr114*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 46 amino acids of the SDHD protein. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with SDHD-related malignant paragangliomas (PMID: 17973943). While no functional studies have been performed to test the effects of this particular variant on SDHD protein function or stability, it deletes 46 C-terminal amino acid residues from the SDHD protein. A founder mutation (p.Leu139Pro) has been reported in this region (PMID: 21348866, 11391798), indicating that the C-terminal amino acid residues may be critical for SDHD function. In summary, this is a rare truncating variant that is expected to disrupt 46 C-terminal amino acids of the SDHD protein, including a region shown to be critical for SDHD protein function. In addition, this variant is absent in the population, and has been reported in an affected individual. For these reasons, this variant has been classified as Pathogenic. |
| Section on Medical Neuroendocrinolgy, |
RCV000505385 | SCV000599543 | pathogenic | Hereditary Paraganglioma-Pheochromocytoma Syndromes | no assertion criteria provided | research |