Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000706069 | SCV000835100 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type VII; Episodic pain syndrome, familial, 3 | 2019-12-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with arginine at codon 699 of the SCN11A protein (p.Gly699Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs145734191, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with painful small fiber neuropathy (PMID: 25791876). ClinVar contains an entry for this variant (Variation ID: 582088). Experimental studies have shown that this missense change exhibits gain-of-function properties (PMID: 25791876). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. |
| Inherited Neuropathy Consortium | RCV000790193 | SCV000929585 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |