Submissions for variant NM_000527.5(LDLR):c.2397_2405del (p.Val800_Leu802del)

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000211657	SCV000295992	likely pathogenic	Familial hypercholesterolemia 1	2016-03-25	criteria provided, single submitter	literature only
Robarts Research Institute,Western University	RCV000211657	SCV000484810	likely pathogenic	Familial hypercholesterolemia 1		criteria provided, single submitter	clinical testing
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000211657	SCV000503485	likely pathogenic	Familial hypercholesterolemia 1	2016-12-16	criteria provided, single submitter	clinical testing	subjects mutated among 2600 FH index cases screened = 8 , family member = 1 with co-segregation / systematically associated with c.1690A>C, p.Asn564His
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000211657	SCV000583949	pathogenic	Familial hypercholesterolemia 1	2017-03-30	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000211657	SCV000588664	pathogenic	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000211657	SCV000607704	pathogenic	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Iberoamerican FH Network	RCV000211657	SCV000748064	pathogenic	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Robarts Research Institute,Western University	RCV000211657	SCV000782941	likely pathogenic	Familial hypercholesterolemia 1	2018-01-02	criteria provided, single submitter	clinical testing
Invitae	RCV001034620	SCV000820238	uncertain significance	Familial hypercholesterolemia	2019-11-08	criteria provided, single submitter	clinical testing	This variant, c.2397_2405delCGTCTTCCT, results in the deletion of 3 amino acids of the LDLR protein (p.Val800_Leu802del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency). This variant has been reported on the same chromosome (in cis) with p.Asn564His in several individuals affected with hypercholesterolemia (PMID: 9147888, 9143924, 12442279, 10090484, 30795984). This variant is also known as 2393del9 in the literature. ClinVar contains entries for this variant (Variation ID: 3737, 226394). Experimental studies have shown that this variant has a mild impact on LDLR protein function. However, when expressed with p.Asn564His in the same cDNA, LDLR receptor function was greatly reduced (PMID: 9143924). 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.
Brunham Lab, Centre for Heart and Lung Innovation,University of British Columbia	RCV000211657	SCV001432566	likely pathogenic	Familial hypercholesterolemia 1	2019-01-27	criteria provided, single submitter	research
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital	RCV000211657	SCV000268667	pathogenic	Familial hypercholesterolemia 1	2012-08-01	no assertion criteria provided	clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum	RCV000211657	SCV000606642	pathogenic	Familial hypercholesterolemia 1		no assertion criteria provided	research