Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000816210 | SCV000956707 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2022-11-08 | 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) performed at Invitae indicates that this missense variant is not expected to disrupt SCN9A protein function. ClinVar contains an entry for this variant (Variation ID: 659238). This missense change has been observed in individual(s) with epilepsy and psychomotor delay (PMID: 31780880). This variant is present in population databases (rs180949263, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1891 of the SCN9A protein (p.Arg1891His). |
Ambry Genetics | RCV002345868 | SCV002653880 | uncertain significance | Inborn genetic diseases | 2021-07-16 | criteria provided, single submitter | clinical testing | The p.R1891H variant (also known as c.5672G>A), located in coding exon 26 of the SCN9A gene, results from a G to A substitution at nucleotide position 5672. The arginine at codon 1891 is replaced by histidine, an amino acid with highly similar properties. This variant was detected in the heterozygous state in an individual with secondary partial epilepsy unresponsive to treatment, psychomotor delay with Rettoid features, and left parieto-occipital type II dysplasia, who also had other variants in epilepsy-associated genes (Fernández-Marmiesse A et al. Front Neurosci, 2019 Nov;13:1135). This amino acid position is not well conserved in available vertebrate species, and histidine is the reference amino acid in other 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. |