ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1274A>T (p.Asn425Ile)

dbSNP: rs879254850
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
LDLR-LOVD, British Heart Foundation RCV000237639 SCV000295336 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Invitae RCV001068739 SCV001233869 likely pathogenic Familial hypercholesterolemia 2023-02-09 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 425 of the LDLR protein (p.Asn425Ile). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with familial hypercholesterolemia (PMID: 21382890; Invitae). This variant is also known as N404I. ClinVar contains an entry for this variant (Variation ID: 251762). 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 expected to disrupt LDLR protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237639 SCV000606379 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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.