Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomic Medicine, |
RCV004701556 | SCV005873486 | pathogenic | not provided | 2025-03-04 | criteria provided, single submitter | clinical testing | |
| Department of Clinical Genetics, |
RCV004003475 | SCV005689611 | pathogenic | Hereditary pheochromocytoma and paraganglioma | 2025-01-24 | criteria provided, single submitter | clinical testing | The following ACMG criteria have been used in classification: PM2_SUP; PVS1_MOD; PS4; PS1 |
| Ce |
RCV004701556 | SCV005434023 | pathogenic | not provided | 2024-10-01 | criteria provided, single submitter | clinical testing | SDHB: PS4, PM2, PS1:Moderate, PVS1:Moderate |
| Gene |
RCV004701556 | SCV005202015 | pathogenic | not provided | 2023-06-26 | criteria provided, single submitter | clinical testing | Initiation codon variant in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Identified in multiple individuals with a personal and/or family history of SDHB-related tumors in published literature (Neumann et al., 2009; Piccini et al., 2012; Sjursen et al., 2013; Bayley et al., 2020; Main et al., 2020); This variant is associated with the following publications: (PMID: 19351833, 23407919, 31492822, 32688340, 24096523, 22241717, 27279923) |
| Myriad Genetics, |
RCV000550393 | SCV004933764 | pathogenic | Pheochromocytoma/paraganglioma syndrome 4 | 2023-12-12 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant is located within the gene translation start codon (p.Met1?) and is predicted to result in abnormal protein translation. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID:28503760, 32688340, 24096523, 28374168]. |
| All of Us Research Program, |
RCV004003475 | SCV004830194 | pathogenic | Hereditary pheochromocytoma and paraganglioma | 2023-06-08 | criteria provided, single submitter | clinical testing | This variant results in the loss of the translation start codon (methionine at codon 1) of the SDHB gene. This variant is expected to disrupt the expression of the full-length SDHB protein. The next in-frame methionine occurs at codon 58, but it is not known if a functional SDHB protein product can be produced using p.Met58 as an alternative translation start site. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with pheochromocytoma/paraganglioma (PMID: 19351833, 22241717, 23407919, 27279923, 27279923, 32688340). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. |
| Color Diagnostics, |
RCV004003475 | SCV004362289 | pathogenic | Hereditary pheochromocytoma and paraganglioma | 2023-05-08 | criteria provided, single submitter | clinical testing | This variant results in the loss of the translation start codon (methionine at codon 1) of the SDHB gene. This variant is expected to disrupt the expression of the full-length SDHB protein. The next in-frame methionine occurs at codon 58, but it is not known if a functional SDHB protein product can be produced using p.Met58 as an alternative translation start site. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with pheochromocytoma/paraganglioma (PMID: 19351833, 22241717, 23407919, 27279923, 27279923, 32688340). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic. |
| MGZ Medical Genetics Center | RCV002289679 | SCV002580781 | pathogenic | Pheochromocytoma | 2022-02-09 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001379744 | SCV001577603 | pathogenic | Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheochromocytoma | 2025-11-05 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator codon of the SDHB mRNA. This change may impact translation initiation or efficiency. The next in-frame methionine is located at codon 58. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with paragangliomas, pheochromocytomas and renal cell carcinomas (PMID: 19351833, 22241717, 23407919, 23512077, 24096523, 25047027, 27279923, 28490599, 29951630). ClinVar contains an entry for this variant (Variation ID: 428932). This variant disrupts the p.Arg46 amino acid residue in SDHB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12618761, 14500403, 15328326, 16314641, 17102082, 18362451, 23083876, 23282968). 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. |
| Ambry Genetics | RCV000492186 | SCV000581214 | pathogenic | Hereditary cancer-predisposing syndrome | 2025-10-03 | criteria provided, single submitter | clinical testing | The p.M1? pathogenic mutation (also known as c.3G>A), located in coding exon 1 of the SDHB gene, results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon (ATG). This alteration has been detected in multiple individuals with paraganglioma and/or pheochromocytoma (Neumann HP et al. Cancer Res. 2009 Apr;69(8):3650-6; Piccini V et al. Endocr. Relat. Cancer 2012 Apr;19(2):149-55; Sjursen W et al. Fam. Cancer 2013 Sep;12(3):529-35; Papathomas TG et al. Eur. J. Endocrinol. 2014 Jan;170:1-12). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the supporting evidence, this variant is interpreted as a disease-causing mutation. |