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

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
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