Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002016515 | SCV002300889 | likely pathogenic | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2023-05-22 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the c.200+5G nucleotide in the SDHB gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 1508994). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 2 of the SDHB gene. It does not directly change the encoded amino acid sequence of the SDHB protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |
| Ambry Genetics | RCV002423248 | SCV002724227 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-29 | criteria provided, single submitter | clinical testing | The c.200+5G>T intronic variant results from a G to T substitution 5 nucleotides after coding exon 2 in the SDHB gene. This nucleotide position is highly conserved in available vertebrate species. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with SDHB-related disease (Ambry internal data). In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |