Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000547767 | SCV000649275 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type 2A; Generalized epilepsy with febrile seizures plus, type 7 | 2018-03-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with serine at codon 517 of the SCN9A protein (p.Gly517Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN9A-related disease. This variant identified in the SCN9A gene is located in the interdomain linker DI/DII region of the resulting protein (PMID: 25348405). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: (SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. |