ClinVar Miner

Submissions for variant NM_000182.5(HADHA):c.173A>G (p.Asn58Ser)

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 RCV002575208 SCV002938468 uncertain significance Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2022-04-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 58 of the HADHA protein (p.Asn58Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with HADHA-related conditions. 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 HADHA protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
CeGaT Center for Human Genetics Tuebingen RCV003418546 SCV004138733 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing HADHA: PM2, BP4
Neuberg Centre For Genomic Medicine, NCGM RCV004577022 SCV005060953 uncertain significance Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency criteria provided, single submitter clinical testing The observed missense c.173A>G(p.Asn58Ser) variant in HADHA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Asn58Ser variant is absent in gnomAD Exomes. This variant has been submitted to the ClinVar database as Uncertain Significance. The amino acid change p.Asn58Ser in HADHA is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Asn at position 58 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS).

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.