ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.1220-8_1227dup

dbSNP: rs2151094080
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001382855 SCV001581804 pathogenic Congenital myasthenic syndrome 4A 2020-02-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the CHRNE protein. Other variant(s) that disrupt this region (p.Y478*) have been determined to be pathogenic (PMID: 12417530). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with congenital myasthenic syndrome (PMID: 29395675). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the CHRNE gene (p.Cys410Profs*51). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 84 amino acids of the CHRNE protein.
Baylor Genetics RCV001382855 SCV004212578 pathogenic Congenital myasthenic syndrome 4A 2023-10-07 criteria provided, single submitter clinical testing
GeneDx RCV004590366 SCV005080802 uncertain significance not provided 2023-06-06 criteria provided, single submitter clinical testing Previously reported in the compound heterozygous state in an individual with congenital myasthenia syndrome; however detailed clinical information was not provided (Durmus et al., 2018); Canonical splice site variant with an unclear effect on protein function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 30290857, 16156036, 29395675)

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