Submissions for variant NM_001365536.1(SCN9A):c.4289G>A (p.Ser1430Asn)

gnomAD frequency: 0.00003  dbSNP: rs201479177

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235275	SCV000293573	uncertain significance	not provided	2015-12-03	criteria provided, single submitter	clinical testing	The S1419N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,200 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 S1419N 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, where amino acids with similar properties to Serine are tolerated across species. In silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae	RCV000817874	SCV000958458	uncertain significance	Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7	2023-08-27	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: 246147). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. This variant is present in population databases (rs201479177, gnomAD 0.005%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1419 of the SCN9A protein (p.Ser1419Asn).
CeGaT Center for Human Genetics Tuebingen	RCV000235275	SCV001746372	uncertain significance	not provided	2021-03-01	criteria provided, single submitter	clinical testing