Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Concord Molecular Medicine Laboratory, |
RCV003325176 | SCV004031052 | likely pathogenic | Congenital myasthenic syndrome 4A; Congenital myasthenic syndrome 4C; Congenital myasthenic syndrome 4B | 2023-08-29 | criteria provided, single submitter | clinical testing | The c.1052C>G missense substitution predicts an amino acid change from from proline to arginine in codon 351 of the CHRNE protein, p.(Pro351Arg). This variant is detected in a compound heterozygous state with another likely pathogenic CHRNE variant (phase not confirmed) in a patient with a clinical diagnosis of congenital myasthenic syndrome. In silico analysis by REVEL suggests this variant to be damaging (REVEL: 0.77). It is located in the critical neurotransmitter-gated ion-channel transmembrane domain (IPR006029). Another amino acid change in the same residue location has been observed in a patient with CMS in trans with another pathogenic variant (PMID: 11408331). This variant is absent in control population (gnomAD). The current evidence allows a classification of this variant as “likely pathogenic” (ACMG criteria: PM1, PM5, PP3_moderate, PM2_supporting, PM3_supporting). |