Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000019060 | SCV004294370 | likely pathogenic | Familial infantile myasthenia | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 506 of the CHAT protein (p.Val506Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with congenital myasthenic syndrome (PMID: 11172068, 26080897). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17508). 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 not expected to disrupt CHAT protein function with a negative predictive value of 95%. Experimental studies have shown that this missense change affects CHAT function (PMID: 11172068). 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. |
| OMIM | RCV000019060 | SCV000039347 | pathogenic | Familial infantile myasthenia | 2001-02-13 | no assertion criteria provided | literature only |