Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000438964 | SCV000536179 | uncertain significance | not provided | 2017-01-30 | criteria provided, single submitter | clinical testing | The T426A variant in the SDCCAG8 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The T426A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret T426A as a variant of uncertain significance. |
Invitae | RCV001368261 | SCV001564648 | uncertain significance | Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 | 2023-08-10 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SDCCAG8-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt SDCCAG8 protein function. ClinVar contains an entry for this variant (Variation ID: 392846). This variant is present in population databases (rs201580075, gnomAD 0.06%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 426 of the SDCCAG8 protein (p.Thr426Ala). |
Fulgent Genetics, |
RCV001368261 | SCV002814422 | uncertain significance | Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 | 2022-02-25 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002522707 | SCV003721229 | uncertain significance | Inborn genetic diseases | 2022-12-01 | criteria provided, single submitter | clinical testing | The c.1276A>G (p.T426A) alteration is located in exon 11 (coding exon 11) of the SDCCAG8 gene. This alteration results from a A to G substitution at nucleotide position 1276, causing the threonine (T) at amino acid position 426 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |