ClinVar Miner

Submissions for variant NM_001365536.1(SCN9A):c.1643G>A (p.Arg548Gln)

gnomAD frequency: 0.00004  dbSNP: rs201247595
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000555619 SCV000649278 uncertain significance Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 548 of the SCN9A protein (p.Arg548Gln). This variant is present in population databases (rs201247595, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. ClinVar contains an entry for this variant (Variation ID: 471088). 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.
Ambry Genetics RCV002404513 SCV002709242 uncertain significance Inborn genetic diseases 2019-10-28 criteria provided, single submitter clinical testing The p.R548Q variant (also known as c.1643G>A), located in coding exon 11 of the SCN9A gene, results from a G to A substitution at nucleotide position 1643. The arginine at codon 548 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is well conserved in available 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.

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