ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.136C>T (p.Arg46Ter) (rs74315370)

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Total submissions: 6
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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
GeneDx 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, Inc,Center for Human Genetics, Inc RCV000660253 SCV000782271 pathogenic Paragangliomas 4 2016-11-01 criteria provided, single submitter clinical testing
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505277 SCV000599486 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research
Gharavi Laboratory,Columbia University RCV000183224 SCV000920697 uncertain significance not provided 2018-09-16 no assertion criteria provided research

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