ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.1326+1G>A

dbSNP: rs1430654625
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München RCV000578225 SCV000680174 likely pathogenic Congenital myasthenic syndrome 4C 2017-09-08 criteria provided, single submitter clinical testing
Invitae RCV002530364 SCV002932430 pathogenic Congenital myasthenic syndrome 4A 2022-03-31 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the CHRNE gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CHRNE-related conditions. ClinVar contains an entry for this variant (Variation ID: 488482). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the CHRNE protein in which other variant(s) (p.Asn452Glufs*4) have been determined to be pathogenic (PMID: 8957026, 15951177, 19064877, 21175599, 28024842, 29054425). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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