Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189527 | SCV000243170 | uncertain significance | not provided | 2014-03-24 | criteria provided, single submitter | clinical testing | p.Arg2142His (CGC>CAC): c.6425 G>A in exon 49 of the SPTAN1 gene (NM_001130438.2) The Arg2142His variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 Arg2142His variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is highly conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. 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 INFANT-EPI,EPILEPSY panel(s). |
Invitae | RCV003765206 | SCV004623938 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2023-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2142 of the SPTAN1 protein (p.Arg2142His). This variant is present in population databases (rs796053324, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SPTAN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 207353). 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. 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. |