Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002349437 | SCV002647902 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-04-15 | criteria provided, single submitter | clinical testing | The c.541-3C>G intronic variant results from a C to G substitution 3 nucleotides upstream from coding exon 6 in the SDHB gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Labcorp Genetics |
RCV003096726 | SCV003206582 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2022-07-21 | criteria provided, single submitter | clinical testing | Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (Invitae). This variant has been observed in individual(s) with autosomal dominant paraganglioma-pheochromocytoma syndromes (Invitae). 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. This sequence change falls in intron 5 of the SDHB gene. It does not directly change the encoded amino acid sequence of the SDHB protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). |