Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001232924 | SCV001405497 | pathogenic | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-09-09 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change falls in intron 1 of the SDHC gene. It does not directly change the encoded amino acid sequence of the SDHC protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. Other variant(s) that result in loss of exon 2 have been determined to be pathogenic (PMID: 19454582; Invitae). This suggests that this variant may also be clinically significant and likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 2 and exons 2-3, but is expected to preserve the integrity of the reading-frame (Invitae). ClinVar contains an entry for this variant (Variation ID: 959549). This variant has been observed in individual(s) with paraganglioma-pheochromocytoma syndromes (Invitae). This variant is not present in population databases (gnomAD no frequency). |