ClinVar Miner

Submissions for variant NM_020549.5(CHAT):c.1642C>T (p.Arg548Ter)

gnomAD frequency: 0.00001  dbSNP: rs369251527
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000552083 SCV000634116 pathogenic Familial infantile myasthenia 2024-01-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg548*) 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). This variant is present in population databases (rs369251527, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with congenital myasthenic syndrome (PMID: 12548525, 29189923). ClinVar contains an entry for this variant (Variation ID: 461449). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003155228 SCV003844879 pathogenic Congenital myasthenic syndrome 2023-02-16 criteria provided, single submitter clinical testing Variant summary: CHAT c.1642C>T (p.Arg548X) 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 cited as pathogenic and disease-associated in ClinVar and HGMD. The variant allele was found at a frequency of 1.6e-05 in 251368 control chromosomes (gnomAD). c.1642C>T has been reported in the literature in individuals affected with Congenital Myasthenic Syndrome (e.g. Maselli_2003, McMacken_2018). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000552083 SCV004215815 pathogenic Familial infantile myasthenia 2024-01-10 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000552083 SCV005676810 pathogenic Familial infantile myasthenia 2024-01-17 criteria provided, single submitter clinical testing

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