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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