Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002470113 | SCV002766420 | likely pathogenic | Congenital myasthenic syndrome | 2022-11-30 | criteria provided, single submitter | clinical testing | Variant summary: CHAT c.451C>T (p.Arg151X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as likely pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251012 control chromosomes. c.451C>T has been reported in the literature in at least one individual affected with congenital heart disease (e.g. Jin_2017, Edwards_2020). These report(s) do not provide conclusions about association of the variant with Congenital Myasthenic Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV002571448 | SCV003459886 | pathogenic | Familial infantile myasthenia | 2022-05-25 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.007%). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with CHAT-related conditions. This sequence change creates a premature translational stop signal (p.Arg151*) in the CHAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHAT are known to be pathogenic (PMID: 12548525, 21786365, 23292760). |
| Baylor Genetics | RCV002571448 | SCV004215817 | likely pathogenic | Familial infantile myasthenia | 2023-05-20 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV003491118 | SCV004232539 | pathogenic | not specified | 2024-01-18 | criteria provided, single submitter | research |