Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001810700 | SCV001477812 | likely pathogenic | not provided | 2020-02-27 | criteria provided, single submitter | clinical testing | The SDHC c.439C>T; p.Gln147Ter variant is reported in the medical literature in an individual with paraganglioma (Schiavi 2005, Schiavi 2006). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant results in a premature termination codon in the last exon of the SDHC gene. While this may not lead to nonsense-mediated decay, it is expected to create a truncated SDHC protein. Based on available information, this variant is considered to be likely pathogenic. References: Schiavi F et al. Predictors and prevalence of paraganglioma syndrome associated with mutations of the SDHC gene. JAMA. 2005 Oct 26;294(16):2057-63. Schiavi F et al. Paraganglioma syndrome: SDHB, SDHC, and SDHD mutations in head and neck paragangliomas. Ann Ny Acad Sci. 2006 1073: 190-197. |
| Invitae | RCV003770468 | SCV004569097 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-07-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln147*) in the SDHC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 23 amino acid(s) of the SDHC protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with SDHC-related conditions (PMID: 16249420). ClinVar contains an entry for this variant (Variation ID: 995676). This variant disrupts a region of the SDHC protein in which other variant(s) (p.Ser151Tyr) have been observed in individuals with SDHC-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |