Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000128877 | SCV000172734 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-28 | criteria provided, single submitter | clinical testing | The c.716_719delCTCT pathogenic mutation, located in coding exon 7 of the SDHB gene, results from a deletion of 4 nucleotides at nucleotide positions 716 to 719, causing a translational frameshift with a predicted alternate stop codon (p.S239Yfs*8). This alteration has previously been detected in individuals diagnosed with pheochromocytoma and paraganglioma (Neumann HP et al. N Engl J Med. 2002 May 9;346(19):1459-66; Vanharanta S et al. Am J Hum Genet. 2004 Jan;74(1):153-9). Of note, this alteration is also designated as 847delTCTC and c.847_50delTCTC in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation. |
| Invitae | RCV001034689 | SCV000644766 | pathogenic | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2023-08-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Ser239Tyrfs*8) in the SDHB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the SDHB protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with pheochromocytoma (PMID: 14685938, 15328326). This variant is also known as 847delTCTC and c.847-50delTCTC. ClinVar contains an entry for this variant (Variation ID: 12782). This variant disrupts the p.Arg242 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 23175444, 25736212, 25972245). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797588 | SCV002041654 | pathogenic | Hereditary pheochromocytoma-paraganglioma | 2021-11-26 | criteria provided, single submitter | clinical testing | Variant summary: SDHB c.716_719delCTCT (p.Ser239TyrfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251460 control chromosomes. c.716_719delCTCT has been reported in the literature in individuals affected with Hereditary Paraganglioma-Pheochromocytoma Syndrome (e.g. Neumann_2002, Vanharanta_2003). These data indicate that the variant is likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| OMIM | RCV000013621 | SCV000033868 | pathogenic | Paragangliomas 4 | 2023-10-17 | no assertion criteria provided | literature only |