Submissions for variant NM_000080.4(CHRNE):c.1072_1091del (p.Pro358fs)

Minimum review status:		Collection method:
Minimum conflict level: Report conflict between different conditions
		ClinVar version:

Total submissions: 5

Download table as spreadsheet

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000641737	SCV000763385	pathogenic	Congenital myasthenic syndrome 4A	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro358Glyfs*32) 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). This variant is present in population databases (no rsID available, gnomAD 0.001%). 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: 534252). For these reasons, this variant has been classified as Pathogenic.
Genetics and Molecular Pathology, SA Pathology	RCV003447547	SCV004175586	pathogenic	Congenital myasthenic syndrome	2021-12-01	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000641737	SCV004212587	pathogenic	Congenital myasthenic syndrome 4A	2024-03-30	criteria provided, single submitter	clinical testing
GeneDx	RCV004702236	SCV005202113	likely pathogenic	not provided	2024-01-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense-mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV004547811	SCV004740563	likely pathogenic	CHRNE-related disorder	2024-03-01	no assertion criteria provided	clinical testing	The CHRNE c.1072_1091del20 variant is predicted to result in a frameshift and premature protein termination (p.Pro358Glyfs*32). To our knowledge, this variant has not been reported in the literature. However, at PreventionGenetics we have observed this variant in the homozygous state in two other patients presenting with myasthenic syndrome phenotypes. This variant is reported in 0.0014% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in CHRNE are expected to be pathogenic. This variant is interpreted as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.