Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001037693 | SCV001201121 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 34 of the SDHAF2 protein (p.Phe34Leu). This variant is present in population databases (rs756917732, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 836537). 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. 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 | RCV002434440 | SCV002746226 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-01 | criteria provided, single submitter | clinical testing | The p.F34L variant (also known as c.100T>C), located in coding exon 2 of the SDHAF2 gene, results from a T to C substitution at nucleotide position 100. The phenylalanine at codon 34 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |