Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV005092376 | SCV005840461 | uncertain significance | Charcot-Marie-Tooth Neuropathy X | 2024-03-03 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 203 of the GJB1 protein (p.Ile203Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GJB1-related conditions (PMID: 9401007, 9566397). ClinVar contains an entry for this variant (Variation ID: 637668). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GJB1 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on GJB1 function (PMID: 30737405). 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 | RCV000789936 | SCV000929321 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |