Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000132150 | SCV000187222 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-10-09 | criteria provided, single submitter | clinical testing | Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation |
Gene |
RCV000183224 | SCV000235644 | pathogenic | not provided | 2018-03-26 | criteria provided, single submitter | clinical testing | This variant is denoted SDHB c.136C>T at the cDNA level and p.Arg46Ter (R46X) at the protein level. The substitution creates a nonsense variant, which changes an Arginine to a premature stop codon (CGA>TGA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in several individuals with a personal and/or family history of paraganglioma (Benn 2003, Brouwers 2006, Srirangalingam 2008, Hensen 2012, Mason 2013, Jochmanova 2017). We consider this variant to be pathogenic. |
Invitae | RCV000228450 | SCV000287758 | pathogenic | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2019-12-19 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg46*) in the SDHB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs74315370, ExAC 0.02%). This variant has been observed in individuals affected with pheochromocytoma, paraganglioma, and renal cell carcinoma (PMID: 12618761, 16405730, 18728283, 21348866, 23797725). ClinVar contains an entry for this variant (Variation ID: 142763). Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic. |
Center for Human Genetics, |
RCV000660253 | SCV000782271 | pathogenic | Paragangliomas 4 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Section on Medical Neuroendocrinolgy, |
RCV000505277 | SCV000599486 | pathogenic | Hereditary Paraganglioma-Pheochromocytoma Syndromes | no assertion criteria provided | research | ||
Gharavi Laboratory, |
RCV000183224 | SCV000920697 | uncertain significance | not provided | 2018-09-16 | no assertion criteria provided | research |