Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000651887 | SCV000773743 | uncertain significance | Neuropathy, hereditary sensory and autonomic, type VII; Episodic pain syndrome, familial, 3 | 2019-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 582 of the SCN11A protein (p.Ala582Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs141228634, ExAC 0.02%), 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 peripheral neuropathy (PMID: 24776970). ClinVar contains an entry for this variant (Variation ID: 541582). Experimental studies have shown that this missense change increases sodium channel activity (PMID: 29213238). 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 | RCV000790195 | SCV000929587 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |