ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1463T>A (p.Ile488Asn)

dbSNP: rs879254913
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000237707 SCV000295447 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000237707 SCV000503351 likely pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 2 , family members = 3 /FH-Fiacenza/Software predictions: Conflicting
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000237707 SCV000583834 pathogenic Hypercholesterolemia, familial, 1 2017-03-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781505 SCV000919587 pathogenic Familial hypercholesterolemia 2024-11-18 criteria provided, single submitter clinical testing Variant summary: LDLR c.1463T>A (p.Ile488Asn) results in a non-conservative amino acid change located in the LDLR class B repeat of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251524 control chromosomes. c.1463T>A has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia (e.g. Garcia-Garcia_2001, Bertolini_2013, Wintjens_2016). Additionally, other missense variants affecting the same codon (I488S, I488T) have been classified on the pathogenic spectrum in ClinVar. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 11668640, 23375686, 26802169). ClinVar contains an entry for this variant (Variation ID: 251856). Based on the evidence outlined above, the variant was classified as 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.