Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute for Genomic Medicine |
RCV006554546 | SCV007449333 | pathogenic | Pheochromocytoma/paraganglioma syndrome 4 | 2024-07-30 | criteria provided, single submitter | clinical testing | This variant is predicted to result in loss of function through nonsense-mediated decay of the encoded transcript or premature truncation of the encoded protein in a gene in which loss of function is a known mechanism of disease (ACMG/AMP: PVS1; PMIDs:19454582, 19802898). This variant has been reported at an elevated frequency in affected individuals/in multiple affected individuals in the literature (ACMG/AMP: PS4_Supporting; PMIDs:20418362, 22723792). This variant is absent from or present at an exceedingly low frequency in gnomAD, a large-scale control population database (ACMG/AMP: PM2). |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003320666 | SCV007109974 | pathogenic | not provided | 2025-06-17 | criteria provided, single submitter | clinical testing | The SDHB c.183T>G (p.Tyr61*) variant causes the premature termination of SDHB protein synthesis. This variant has been reported in the published literature in individuals affected with pheochromocytoma/paraganglioma (PMID: 28374168 (2017), 20418362 (2010)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. |
| Gene |
RCV003320666 | SCV004025581 | pathogenic | not provided | 2025-05-28 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19958924, 31492822, 22723792, 28374168, 34439168, 20418362) |
| Ambry Genetics | RCV002413384 | SCV002717032 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-12-18 | criteria provided, single submitter | clinical testing | The p.Y61* pathogenic mutation (also known as c.183T>G), located in coding exon 2 of the SDHB gene, results from a T to G substitution at nucleotide position 183. This changes the amino acid from a tyrosine to a stop codon within coding exon 2. This alteration has been detected in multiple individuals diagnosed with a paraganglioma or pheochromocytoma (Lodish MB et al. Endocr Relat Cancer. 2010 Sep;17:581-8; Jochmanova I et al. J Cancer Res Clin Oncol. 2017 Aug;143:1421-1435; Ambry internal data). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| MGZ Medical Genetics Center | RCV002289690 | SCV002579716 | pathogenic | Pheochromocytoma | 2021-12-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001389812 | SCV001591295 | pathogenic | Gastrointestinal stromal tumor; Pheochromocytoma/paraganglioma syndrome 4; Pheochromocytoma | 2025-05-05 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr61*) in the SDHB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with paraganglioma (PMID: 20418362). ClinVar contains an entry for this variant (Variation ID: 438412). For these reasons, this variant has been classified as Pathogenic. |
| Section on Medical Neuroendocrinolgy, |
RCV000505331 | SCV000599487 | pathogenic | Hereditary pheochromocytoma and paraganglioma | no assertion criteria provided | research |