Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000485087 | SCV000568692 | pathogenic | not provided | 2021-09-22 | criteria provided, single submitter | clinical testing | Published functional studies indicate cells harboring the R43W variant result in AChR deficiency at the neuromuscular junction (Azuma et al., 2015); Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22678886, 25264167) |
| Labcorp Genetics |
RCV000805114 | SCV000945058 | likely pathogenic | Lethal multiple pterygium syndrome | 2024-12-02 | 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 43 of the CHRND protein (p.Arg43Trp). This variant is present in population databases (rs55868108, gnomAD 0.009%). This missense change has been observed in individual(s) with autosomal recessive congenital myasthenic syndrome (PMID: 25264167). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 420109). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CHRND protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CHRND function (PMID: 25264167). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Revvity Omics, |
RCV000485087 | SCV002019297 | pathogenic | not provided | 2019-07-10 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001332575 | SCV001524945 | uncertain significance | Congenital myasthenic syndrome 3A | 2019-07-14 | flagged submission | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |