ClinVar Miner

Submissions for variant NM_015512.5(DNAH1):c.5740G>A (p.Glu1914Lys)

gnomAD frequency: 0.00056  dbSNP: rs199740667
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000687132 SCV000814684 uncertain significance Spermatogenic failure 18; Ciliary dyskinesia, primary, 37 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1914 of the DNAH1 protein (p.Glu1914Lys). This variant is present in population databases (rs199740667, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DNAH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 567136). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DNAH1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
UNC Molecular Genetics Laboratory, University of North Carolina at Chapel Hill RCV001580357 SCV001810040 uncertain significance Primary ciliary dyskinesia 2020-07-02 criteria provided, single submitter clinical testing
Johns Hopkins Genomics, Johns Hopkins University RCV003229599 SCV003927226 uncertain significance Ciliary dyskinesia, primary, 37 2023-04-07 criteria provided, single submitter clinical testing This DNAH1 missense variant (rs199740667) is rare (<0.1%) in a large population dataset (gnomAD v2.1.1: 196/280214 total alleles; 0.07%; no homozygotes). It has been reported in ClinVar (Variation ID 567136), but not in the literature, to our knowledge. Two bioinformatic tools queried predict that this substitution would be damaging, and the glutamic acid residue at this position is evolutionarily conserved across many of the species assessed. The contribution of DNAH1 to primary ciliary dyskinesia has not been confirmed. We consider the clinical significance of c.5740G>A; p.Glu1914Lys in DNAH1 to be uncertain at this time.

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.