Submissions for variant NM_000527.5(LDLR):c.1510A>G (p.Lys504Glu) (rs730882103)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000237290	SCV000295475	likely benign	Familial hypercholesterolemia 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	RCV000237290	SCV000503360	uncertain significance	Familial hypercholesterolemia 1	2016-12-16	criteria provided, single submitter	clinical testing	subject mutated among 2600 FH index cases screened = 1/Software predictions: Benign
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000237290	SCV000583841	pathogenic	Familial hypercholesterolemia 1	2017-03-30	criteria provided, single submitter	clinical testing
Fundacion Hipercolesterolemia Familiar	RCV000237290	SCV000607606	uncertain significance	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Color	RCV001175675	SCV001339364	uncertain significance	Familial hypercholesterolemia	2019-05-30	criteria provided, single submitter	clinical testing
Dept. of Genetics and Pharmacogenomics, Merck Research Labs	RCV000161990	SCV000189565	not provided	not provided		no assertion provided	in vitro
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum	RCV000237290	SCV000606446	benign	Familial hypercholesterolemia 1		no assertion criteria provided	research
Broad Institute Rare Disease Group,Broad Institute	RCV001175675	SCV001422594	uncertain significance	Familial hypercholesterolemia	2020-01-22	no assertion criteria provided	curation	The p.Lys504Glu variant in LDLR has been reported in 1 Italian and 2 Norwegian individuals with familial hypercholesterolemia (PMID: 25647241, PMID: 15199436), but has been identified in 0.003% (3/113736) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs730882103). This variant has also been reported in ClinVar as having conflicint interpretations of pathogenicity (Variation ID: rs730882103). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PS4_supporting (Richards 2015).