Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000531338 | SCV000654747 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type VII; Episodic pain syndrome, familial, 3 | 2017-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with arginine at codon 1535 of the SCN11A protein (p.Lys1535Arg). The lysine residue is weakly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SCN11A-related disease. 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 arginine 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 RNA splicing and protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Inherited Neuropathy Consortium | RCV001027471 | SCV001190041 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | provider interpretation |