ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.79C>T (p.Arg27Ter) (rs74315369)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129929 SCV000184747 pathogenic Hereditary cancer-predisposing syndrome 2017-07-20 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000471400 SCV000554026 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2018-09-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg27*) in the SDHB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs74315369, ExAC 0.006%). This variant has been observed in individuals affected with pheochromocytoma (PMID: 12000816, 25215250, 12362046), paraganglioma (PMID: 18382370, 14685938, 19415531), and early-onset renal cell cancer (PMID: 14685938). This variant is also known as C213T in the literature. ClinVar contains an entry for this variant (Variation ID: 12783). Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000657585 SCV000779322 pathogenic not provided 2018-05-29 criteria provided, single submitter clinical testing This variant is denoted SDHB c.79C>T at the cDNA level and p.Arg27Ter (R27X) 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. Also published as SDHB 213C>T using alternate nomenclature, this variant has been reported in several individuals with pheochromocytoma and/or paraganglioma as well as in at least one individual with early-onset renal cell carcinoma (Casc?n 2002, Neumann 2004, Vanharanta 2004, Klein 2008, Naito 2009, Merlo 2013, Graham 2014, Jochmanova 2017). We consider SDHB Arg27Ter to be pathogenic.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000013623 SCV000840069 pathogenic Paragangliomas 4 2018-02-06 criteria provided, single submitter clinical testing This c.79C>T (p.R27*) variant is predicted to result in a premature stop codon and has been reported in individuals with pheochromocytoma, paraganglioma and early-onset renal cell cancer (PMID: 12000816, 25215250, 18382370, 14685938, 14685938). In addition, in vitro studies have shown that the c.79C>T (p.R27*) variant alters SDHB expression and function. Therefore we classify this variant as pathogenic.
OMIM RCV000013623 SCV000033870 pathogenic Paragangliomas 4 2002-05-09 no assertion criteria provided literature only
OMIM RCV000013624 SCV000033871 pathogenic Pheochromocytoma 2002-05-09 no assertion criteria provided literature only
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505368 SCV000599488 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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