Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001230036 | SCV001402503 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 1 of the SDHC gene. It does not directly change the encoded amino acid sequence of the SDHC protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs760206414, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 957116). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). RNA analysis provides insufficient evidence to determine the effect of this variant on SDHC splicing (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. |
Ambry Genetics | RCV004032688 | SCV005020186 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-14 | criteria provided, single submitter | clinical testing | The c.20+5C>T intronic variant results from a C to T substitution 5 nucleotides after coding exon 1 in the SDHC gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV004590253 | SCV005080327 | uncertain significance | not provided | 2023-12-21 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this variant does not alter splicing; Has not been previously published as pathogenic or benign to our knowledge |