Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001041707 | SCV001205337 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma | 2023-06-27 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 839853). This variant has not been reported in the literature in individuals affected with SDHB-related conditions. Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 24 of the SDHB protein (p.Gln24Pro). |
| Ambry Genetics | RCV003160276 | SCV003860452 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-27 | criteria provided, single submitter | clinical testing | The c.71_72delAGinsCC variant (also known as p.Q24P), located in coding exon 1 of the SDHB gene, results from an in-frame deletion of AG and insertion of CC at nucleotide positions 71 to 72. This results in the substitution of the glutamine residue for a proline residue at codon 24, an amino acid with similar properties. However, this change occurs in the last two base pairs of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. Using the BDGP splice site prediction tool, this alteration is predicted abolish the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). In addition, as an indel resulting in a missense substitution, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV003442155 | SCV004169302 | uncertain significance | not provided | 2023-04-05 | 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 protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |