Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001959033 | SCV002238762 | pathogenic | Congenital myasthenic syndrome 4A | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 238 of the CHRNE protein (p.Arg238Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of autosomal recessive congenital myasthenic syndrome (PMID: 29367459; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as R218W. ClinVar contains an entry for this variant (Variation ID: 1459509). 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) performed at Invitae indicates that this missense variant is expected to disrupt CHRNE protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CHRNE function (PMID: 29367459). For these reasons, this variant has been classified as Pathogenic. |
Baylor Genetics | RCV001959033 | SCV004212574 | pathogenic | Congenital myasthenic syndrome 4A | 2023-10-16 | criteria provided, single submitter | clinical testing |