ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.713del (p.Phe238fs) (rs876660642)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221959 SCV000278246 pathogenic Hereditary cancer-predisposing syndrome 2019-01-29 criteria provided, single submitter clinical testing The c.713delT pathogenic mutation, located in coding exon 7 of the SDHB gene, results from a deletion of one nucleotide at nucleotide position 713, causing a translational frameshift with a predicted alternate stop codon (p.F238Sfs*10). This mutation has been identified in several individuals with paraganglioma (PGL) and/or pheochromocytoma (PCC) (Benn DE et al. J. Clin. Endocrinol. Metab. 2006 Mar;91(3):827-36; Burnichon N et al. J. Clin. Endocrinol. Metab. 2009 Aug;94(8):2817-27; Rijken JA et al. Clin. Genet. 2018 Jan;93:60-66). In addition, loss of heterozygosity at the SDHB locus was established in the tumor of a germline carrier of this mutation (Burnichon N et al. J. Clin. Endocrinol. Metab. 2009 Aug;94(8):2817-27). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation. As such, this alteration is interpreted as a disease-causing mutation.
Invitae RCV001233559 SCV001406160 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2019-07-17 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SDHB gene (p.Phe238Serfs*10). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 43 amino acids of the SDHB protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with paraganglioma-pheochromocytoma syndromes (PMID: 28490599, 19454582, 16317055, 22517554). This variant is also known as c.713delT (p.Phe238fs) in the literature. ClinVar contains an entry for this variant (Variation ID: 233795). This variant disrupts the C-terminus of the SDHB protein. Other variant(s) that disrupt this region (p.Leu240Serfs*16) have been determined to be pathogenic (Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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