Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001381306 | SCV001579629 | pathogenic | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2020-07-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp138Ilefs*6) in the SDHB 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 observed in individual(s) with pheochromocytoma (PMID: 22517554). This variant is also known as c.411del in the literature. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002329400 | SCV002628545 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-21 | criteria provided, single submitter | clinical testing | The c.412delG pathogenic mutation, located in coding exon 4 of the SDHB gene, results from a deletion of one nucleotide at nucleotide position 412, causing a translational frameshift with a predicted alternate stop codon (p.D138Ifs*6). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |