Submissions for variant NM_000080.4(CHRNE):c.1319_1326+15del

dbSNP: rs1208462125

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000821188	SCV000961937	pathogenic	Congenital myasthenic syndrome 4A	2023-09-05	criteria provided, single submitter	clinical testing	Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). This variant results in the deletion of part of exon 11 (c.1319_1326+15del) 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. 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 been observed in individual(s) with congenital myasthenic syndrome (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 663330). 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.
CeGaT Center for Human Genetics Tuebingen	RCV000996453	SCV001151159	likely pathogenic	not provided	2018-07-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000821188	SCV004214239	pathogenic	Congenital myasthenic syndrome 4A	2023-12-14	criteria provided, single submitter	clinical testing