ClinVar Miner

Submissions for variant NM_003000.2(SDHB):c.717dup (p.Leu240fs) (rs1060503764)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000475105 SCV000554018 pathogenic Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma 2018-07-06 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SDHB gene (p.Leu240Serfs*16). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acids of the SDHB protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SDHB-related disease. ClinVar contains an entry for this variant (Variation ID: 412481). A different truncation (deletion of exon 8) that lies downstream of this variant has been determined to be pathogenic (Invitae). This suggests that deletion of this region of the SDHB protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000492377 SCV000581212 pathogenic Hereditary cancer-predisposing syndrome 2015-11-10 criteria provided, single submitter clinical testing The c.717dupT pathogenic mutation, located in coding exon 7 of the SDHB gene, results from a duplication of T at nucleotide position 717, causing a translational frameshift with a predicted alternate stop codon. Similar alterations have been reported in this region in individuals with PCCs and PGLs (AmarL, J et al.Clin.Oncol. 2005 Dec; 23(34):8812-8;Neumann HP et al.Cancer Res. 2009 Apr; 69(8):3650-6;Lima J et al.J.Clin.Endocrinol.Metab. 2007 Dec; 92(12):4853-64). In addition to the evidence presented in the literature, since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

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