Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000690559 | SCV000818247 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2020-02-17 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glycine at codon 1033 of the SCN9A protein (p.Ala1033Gly). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and glycine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SCN9A-related disease. This variant is not present in population databases (ExAC no frequency). |