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 2017-07-19 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: 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
Center for Human Genetics, Inc RCV000660253 SCV000782271 pathogenic Paragangliomas 4 2016-11-01 criteria provided, single submitter clinical testing
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.
Gharavi Laboratory,Columbia University RCV000183224 SCV000920697 uncertain significance not provided 2018-09-16 no assertion criteria provided research
Invitae RCV000228450 SCV000287758 pathogenic Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 46 (p.Arg46*) of 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. This particular variant has been reported in the literature in individuals affected with pheochromocytoma, paraganglioma, and renal cell carcinoma (PMID: 12618761, 16405730, 18728283, 21348866, 23797725). For these reasons, this variant has been classified as Pathogenic.
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505277 SCV000599486 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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