Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189504 | SCV000243147 | uncertain significance | not provided | 2014-03-12 | criteria provided, single submitter | clinical testing | p.Arg1083His (CGT>CAT): c.3248 G>A in exon 24 of the SPTAN1 gene (NM_001130438.2) The R1083H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R1083H variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R1083H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts that R1083H is probably damaging to the protein structure/function. However, previously reported pathogenic mutations in SPTAN1 include in-frame deletions or duplications located within the last four spectrin repeats of the protein, which are essential for dimerization (Saitsu et al., 2010), and the Arg1083 residue is outside this region. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in EPILEPSY panel(s). |
Invitae | RCV001857657 | SCV002178430 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-08-17 | 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SPTAN1 protein function. ClinVar contains an entry for this variant (Variation ID: 207331). This variant has not been reported in the literature in individuals affected with SPTAN1-related conditions. This variant is present in population databases (rs369611161, gnomAD 0.004%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1083 of the SPTAN1 protein (p.Arg1083His). |