Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000801877 | SCV000941675 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-09-19 | criteria provided, single submitter | clinical testing | 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: 647376). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. This variant is present in population databases (rs778449586, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 4 of the SDHAF2 protein (p.Ser4Cys). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. |
Ambry Genetics | RCV001010273 | SCV001170445 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-03 | criteria provided, single submitter | clinical testing | The p.S4C variant (also known as c.11C>G), located in coding exon 1 of the SDHAF2 gene, results from a C to G substitution at nucleotide position 11. The serine at codon 4 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV003472368 | SCV004202957 | uncertain significance | Paragangliomas 2 | 2022-12-30 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000801877 | SCV004826867 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-04-27 | criteria provided, single submitter | clinical testing |