ClinVar Miner

Submissions for variant NM_020549.5(CHAT):c.243G>A (p.Trp81Ter)

gnomAD frequency: 0.00001  dbSNP: rs1384661323
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001779473 SCV002014907 uncertain significance not specified 2021-10-14 criteria provided, single submitter clinical testing Variant summary: CHAT c.243G>A (p.Trp81X) results in a premature termination codon located in exon 1 (NM_020549.4) of the gene. An alternate translation initiation codon exists in exon 2 of the gene which gives rise to a protein product found to be most abundantly expressed in human tissues. Contrary, the protein product including exon 1 is found to be expressed at low levels (Misawa_1997). In agreement, data from GTEx Portal indicate that exon 1 is not expressed or is minimally expressed in various human tissue sites studied. The variant allele was found at a frequency of 7e-06 in 142118 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.243G>A in individuals affected with Congenital Myasthenic Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Other loss-of-function variants located in exon 1 of the gene are cited in ClinVar by multiple submitters (evaluation after 2014) as uncertain significance (Variation IDs: 949501, 575316, 954911). Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV002034537 SCV002285532 uncertain significance Familial infantile myasthenia 2021-07-14 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp81*) in the CHAT gene. However, it is currently unclear if variants that occur in this region of the gene cause disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with CHAT-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV002034537 SCV004215799 likely pathogenic Familial infantile myasthenia 2023-10-15 criteria provided, single submitter clinical testing

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