Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001317748 | SCV001508419 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2023-06-04 | 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: 1018448). This variant has not been reported in the literature in individuals affected with SCN9A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1399 of the SCN9A protein (p.Ile1399Phe). |
Mayo Clinic Laboratories, |
RCV001508458 | SCV001714616 | uncertain significance | not provided | 2019-06-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002329274 | SCV002628582 | uncertain significance | Inborn genetic diseases | 2021-06-12 | criteria provided, single submitter | clinical testing | The p.I1399F variant (also known as c.4195A>T), located in coding exon 22 of the SCN9A gene, results from an A to T substitution at nucleotide position 4195. The isoleucine at codon 1399 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |