ClinVar Miner

Submissions for variant NM_020549.4(CHAT):c.1840-9A>G (rs1279554995)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497993 SCV000589833 likely pathogenic not provided 2017-09-07 criteria provided, single submitter clinical testing The c.1840-9 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Several in silico prediction models predict c.1840-9 A>G may create a new splice acceptor site in intron 13 and lead to abnormal gene splicing. However, in the absence of RNA/functional studies the actual effect of this sequence change is unknown.
Invitae RCV000688376 SCV000815984 uncertain significance Familial infantile myasthenia 2018-04-25 criteria provided, single submitter clinical testing This sequence change falls in intron 13 of the CHAT gene. It does not directly change the encoded amino acid sequence of the CHAT protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHAT-related disease. ClinVar contains an entry for this variant (Variation ID: 432145). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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