Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000215091 | SCV000279165 | uncertain significance | not provided | 2016-03-22 | criteria provided, single submitter | clinical testing | The I62V variant has been reported previously in a Hispanic patient with febrile seizures (Singh et al., 2009). The patient was a heterozygous carrier of this variant; however, family studies were not performed. The I62V variant was not identified in 276 ethnically matched control chromosomes (Singh et al., 2009). The I62V variant was not observed in approximately 6,400 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 I62V 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 conserved across species, and 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 variant or a rare benign variant. |
| Invitae | RCV000555200 | SCV000649284 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 62 of the SCN9A protein (p.Ile62Val). This variant is present in population databases (rs121908920, gnomAD 0.006%). This missense change has been observed in individual(s) with febrile seizures (PMID: 19763161). ClinVar contains an entry for this variant (Variation ID: 6368). 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 with a negative predictive value of 95%. 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. |
| Fulgent Genetics, |
RCV000765531 | SCV000896845 | uncertain significance | Primary erythromelalgia; Neuropathy, hereditary sensory and autonomic, type 2A; Paroxysmal extreme pain disorder; Severe myoclonic epilepsy in infancy; Channelopathy-associated congenital insensitivity to pain, autosomal recessive; Generalized epilepsy with febrile seizures plus, type 7 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002408455 | SCV002711497 | uncertain significance | Inborn genetic diseases | 2020-03-20 | criteria provided, single submitter | clinical testing | The p.I62V variant (also known as c.184A>G), located in coding exon 1 of the SCN9A gene, results from an A to G substitution at nucleotide position 184. The isoleucine at codon 62 is replaced by valine, an amino acid with highly similar properties. This variant has been detected in an individual with febrile seizures (Singh NA et al. PLoS Genet, 2009 Sep;5:e1000649). This amino acid position is well conserved in available vertebrate species; however, valine is the reference amino acid in other vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| OMIM | RCV000006740 | SCV000026932 | uncertain significance | Febrile seizures, familial, 3b | 2009-09-01 | no assertion criteria provided | literature only |