ClinVar Miner

Submissions for variant NM_003002.4(SDHD):c.64C>T (p.Arg22Ter) (rs104894306)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000492341 SCV000581232 pathogenic Hereditary cancer-predisposing syndrome 2016-02-04 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)
GeneDx RCV000657641 SCV000779386 pathogenic not provided 2017-02-22 criteria provided, single submitter clinical testing This variant is denoted SDHD c.64C>T at the cDNA level and p.Arg22Ter (R22X) 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 multiple individuals and families with hereditary paraganglioma/pheochromocytoma (Gimenez-Roqueplo 2001, Taschner 2001, Amar 2005, Lefebvre 2012, Piccini 2012) and is considered pathogenic.
Genetic Services Laboratory, University of Chicago RCV000193132 SCV000248840 pathogenic Pheochromocytoma 2014-01-23 criteria provided, single submitter clinical testing
Invitae RCV000641048 SCV000762666 pathogenic Paraganglioma and gastric stromal sarcoma; Pheochromocytoma; Paragangliomas 1; Cowden syndrome 3 2018-12-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg22*) in the SDHD gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in many individuals and families affected with paraganglioma and/or pheochromocytoma (PMID: 21348866, 11391798, 16317055, 11605159, 19258401, 22241717, 22517554). In addition, it has been reported to segregate with paraganglioma in a single family (PMID: 11605159). ClinVar contains an entry for this variant (Variation ID: 6903). Loss-of-function variants in SDHD are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000007312 SCV000027509 pathogenic Paragangliomas 1 2001-12-01 no assertion criteria provided literature only

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