ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.716_719delCTCT (rs587781266)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000128877 SCV000172734 pathogenic Hereditary cancer-predisposing syndrome 2017-04-27 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)
Invitae RCV000013621 SCV000644766 pathogenic Paragangliomas 4 2017-04-16 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotides from exon 7 of the SDHB mRNA (c.716_719delCTCT), causing a frameshift at codon 239. This creates a premature translational stop signal in the penultimate exon of the SDHB mRNA (p.Ser239Tyrfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid residues of the SDHB protein. This variant is not present in population databases (rs587781266, ExAC no frequency). This variant has been reported in individuals affected with pheochromocytoma (PMID: 15328326) and to segregate with paraganglioma and renal cell carcinoma in a single family (PMID: 14685938). This variant is also known as 847delTCTC and c.847-50delTCTC in the literature. ClinVar contains an entry for this variant (Variation ID: 12782). Several missense substitutions at codon 242 (p.Arg242His, p.Arg242Cys, and p.Arg242Ser) have been determined to be pathogenic (PMID: 25972245, 25736212, 23175444, 23175444). This suggests that the arginine residue is critical for SDHB protein function and that other variants that disrupt this position, including this frameshift variant, are also pathogenic. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000013621 SCV000033868 pathogenic Paragangliomas 4 2002-05-09 no assertion criteria provided literature only
OMIM RCV000013622 SCV000033869 pathogenic Pheochromocytoma 2002-05-09 no assertion criteria provided literature only

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