Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001202796 | SCV001373923 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2019-10-05 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with SDHB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the SDHB gene (p.Ile263Metfs*7). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 18 amino acids of the SDHB protein. |
| Ambry Genetics | RCV002418670 | SCV002681088 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-04-25 | criteria provided, single submitter | clinical testing | The c.789delT variant, located in coding exon 8 of the SDHB gene, results from a deletion of one nucleotide at nucleotide position 789, causing a translational frameshift with a predicted alternate stop codon (p.I263Mfs*7). This alteration occurs at the 3' terminus of theSDHB gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 18 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). Based on internal structural analysis, the variant disrupts the protein-protein interaction (Inaoka DK et al. Int J Mol Sci, 2015 Jul;16:15287-308). In addition, multiple similar truncating alterations have been observed in individuals with a paraganglioma (Neumann HP et al. Cancer Res, 2009 Apr;69:3650-6; Rattenberry E et al. J Clin Endocrinol Metab, 2013 Jul;98:E1248-56; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |