ClinVar Miner

Submissions for variant NM_000080.4(CHRNE):c.1192C>T (p.Gln398Ter)

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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 RCV003085244 SCV003485054 pathogenic Congenital myasthenic syndrome 4A 2023-06-10 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln398*) in the CHRNE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHRNE are known to be pathogenic (PMID: 22678886). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 2170253). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005021570 SCV005644252 likely pathogenic Congenital myasthenic syndrome 4A; Congenital myasthenic syndrome 4C; Congenital myasthenic syndrome 4B 2024-06-17 criteria provided, single submitter clinical testing
Neurogenomics Lab, Neuroscience Institute, University Of Cape Town RCV005098886 SCV005849066 pathogenic Congenital myasthenic syndrome 4 2025-02-10 criteria provided, single submitter research The highest population allele frequency of this variant in gnomAD v4.0 is 0.000011 (0.001%; 1/90660 alleles in the South Asian population). PM3_Strong: 1.5 points: 0.5 points awarded for homozygous observation of variant in proband under assessment, 1 point awarded for a compound heterozygous observation of the variant with another pathogenic CHRNE variant (confirmed in trans) and 0.5 points awarded for a compound heterozygous observation of the variant with another pathogenic CHRNE variant (not confirmed in trans) (PMID: 29395675)- both observations are in probands with consistent phenotype for disorder. PVS1_Strong: nonsense variant, predicted to undergo NMD, exon is present in biologically-relevant transcript. Loss of function variation in CHRNE is a reported disease mechanism (PMID 22678886). Sequencing funded by the International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD): https://www.ucl.ac.uk/genomic-medicine-neuromuscular-diseases/.

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