Submissions for variant NM_000527.5(LDLR):c.806G>A (p.Gly269Asp)

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Cardiovascular Biomarker Research Laboratory,Mayo Clinic	RCV000210247	SCV000266316	likely benign	Familial hypercholesterolemia 1	2015-08-31	criteria provided, single submitter	research	MAF =<0.3%. "Little/No effect" on the LDL receptor activity based on experimental validation.
LDLR-LOVD, British Heart Foundation	RCV000210247	SCV000294983	likely benign	Familial hypercholesterolemia 1	2016-03-25	criteria provided, single submitter	literature only
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000210247	SCV000322915	likely benign	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research	0/212 non-FH alleles
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000210247	SCV000503239	likely benign	Familial hypercholesterolemia 1	2016-12-16	criteria provided, single submitter	clinical testing	subjects mutated among 2600 FH index cases screened = 3 / FH-Rome-3 / Software predictions: Conflicting
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000210247	SCV000583743	likely pathogenic	Familial hypercholesterolemia 1	2017-03-30	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000210247	SCV000588518	likely benign	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000210247	SCV000607503	likely benign	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Integrated Genetics/Laboratory Corporation of America	RCV000161966	SCV000697252	benign	not provided	2016-03-11	criteria provided, single submitter	clinical testing	Variant summary: c.806G>A affects a non-conserved nucleotide, resulting in amino acid change from Gly to Asp. 2/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). Functional study showed that the LDL uptake, binding capacity of LDL, and LDLR expression of variant were similar to those observed in control cells (Etxebarria_2012), indicating the neutral effect. This variant was found in 24/131566 control chromosomes at a frequency of 0.0001824. This variant has been reported in multiple FH patients without strong evidence for causality. Among the reported patients, variant was reported to co-occur with a deleterious LDLR variant c.1045delC in cis (Mozas_2004) and there is at least one family reported with lack of co-segregation of this variant with disease (Bourbon_2008). In addition, variant has been detected in early-onset myocardial infarction case with comparable allele frequency as in controls and multiple publications listed variant as nonpathogenic/benign (Do_2015, Etxebarre_2012, and Benito-Vicente_2015). Considering all, this variant is classified as Benign.
Invitae	RCV000775049	SCV000752451	likely benign	Familial hypercholesterolemia	2019-12-31	criteria provided, single submitter	clinical testing
Color	RCV000775049	SCV000909148	likely benign	Familial hypercholesterolemia	2018-07-10	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000210247	SCV001282942	uncertain significance	Familial hypercholesterolemia 1	2018-03-08	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Dept. of Genetics and Pharmacogenomics, Merck Research Labs	RCV000161966	SCV000189541	not provided	not provided		no assertion provided	in vitro
CSER _CC_NCGL, University of Washington	RCV000148586	SCV000190300	uncertain significance	Hypercholesterolaemia	2014-06-01	no assertion criteria provided	research
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum	RCV000210247	SCV000606229	pathogenic	Familial hypercholesterolemia 1		no assertion criteria provided	research
Iberoamerican FH Network	RCV000210247	SCV000748174	likely benign	Familial hypercholesterolemia 1	2016-03-01	no assertion criteria provided	research