ClinVar Miner

Submissions for variant NM_144772.3(NAXE):c.326dup (p.Thr110fs)

dbSNP: rs779820587
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000785167 SCV000923734 uncertain significance Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 2019-01-01 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV001267663 SCV001445887 pathogenic Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy 2019-05-02 criteria provided, single submitter clinical testing This frameshifting variant in exon 3 of 6 introduces a premature stop codon and is therefore predicted to result in loss of normal protein function. This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is present in the heterozygous state in the gnomAD population database at a frequency of 0.002% (6/251464) and thus is presumed to be rare. Based on the predicted consequence of the variant and phenotypic overlap, the c.326dup (p.Thr110TyrfsTer11) variant is classified as Pathogenic.
Revvity Omics, Revvity RCV000785167 SCV002017696 pathogenic Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1 2019-11-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001873197 SCV002163748 pathogenic not provided 2023-05-23 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 634634). This variant has not been reported in the literature in individuals affected with NAXE-related conditions. This variant is present in population databases (rs779820587, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Thr110Tyrfs*11) in the NAXE gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NAXE are known to be pathogenic (PMID: 27290639, 27616477, 33798445).
PreventionGenetics, part of Exact Sciences RCV003411725 SCV004108501 likely pathogenic NAXE-related disorder 2023-06-19 criteria provided, single submitter clinical testing The NAXE c.326dupC variant is predicted to result in a frameshift and premature protein termination (p.Thr110Tyrfs*11). This variant was reported in an individual with Congenital heart disease (Edwards et al 2020. PubMed ID: 32368696). This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-156562185-G-GC). Frameshift variants in NAXE 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.