ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.343C>T (p.Arg115Ter) (rs751000085)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000178185 SCV000230200 pathogenic not provided 2015-05-04 criteria provided, single submitter clinical testing
Invitae RCV000627752 SCV000644757 pathogenic Gastrointestinal stroma tumor; Paragangliomas 4; Pheochromocytoma 2018-06-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg115*) in the SDHB gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs751000085, ExAC 0.003%). This variant has been reported in two families and several individuals affected with paraganglioma and/or pheochromocytoma (PMID: 16405730, 24523625, 25047027,21348866, 28490599). ClinVar contains an entry for this variant (Variation ID: 197210). Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000505340 SCV000711787 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes 2016-06-22 criteria provided, single submitter clinical testing The p.Arg115X variant in SDHB has been reported in at least two individuals with hereditary paragangliomas and pheochromocytomas and segregated with disease in 1 affected relative (Bayley 2006, Benn 2006, Lefebvre 2006). It has also been id entified in 2/66740 European chromosomes by the Exome Aggregation Consortium (Ex AC, http://exac.broadinstitute.org; dbSNP rs751000085). This frequency is low en ough to be consistent with the frequency of hereditary paragangliomas and pheoch romocytomas in the general population. This nonsense variant is predicted to res ult in a premature termination codon at position 115, leading to a truncated or absent protein. Heterozygous loss-of-function variants in the SDHB gene are asso ciated with hereditary paragangliomas and pheochromocytomas. In summary, this va riant meets our criteria to be classified as pathogenic for hereditary paragangl iomas and pheochromocytomas in an autosomal dominant manner based on the predict ed impact to the protein and low frequency in controls.
Section on Medical Neuroendocrinolgy,National Institutes of Health RCV000505340 SCV000599499 pathogenic Hereditary Paraganglioma-Pheochromocytoma Syndromes no assertion criteria provided research

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