Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002241201 | SCV001384051 | pathogenic | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2019-09-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the SDHD protein. Other variant(s) that disrupt this region (p.Asp113Metfs*21, p.Ser132Glnfs*3, Leu139Pro) have been determined to be pathogenic (PMID: 12111639, 27539324,22517554, 21348866, 17848412, 11391798). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with SDHD-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the SDHD gene (p.Ser68Argfs*45). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 92 amino acids of the SDHD protein. |