Submissions for variant NM_000527.5(LDLR):c.693C>A (p.Cys231Ter)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000003928	SCV000294914	pathogenic	Familial hypercholesterolemia 1	2016-03-25	criteria provided, single submitter	literature only
Robarts Research Institute,Western University	RCV000003928	SCV000484681	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	RCV000003928	SCV000503223	pathogenic	Familial hypercholesterolemia 1	2016-12-16	criteria provided, single submitter	clinical testing	subjects mutated among 2600 FH index cases screened = 4 , family members = 9 with co-segregation
Molecular Genetics Laboratory,Centre for Cardiovascular Surgery and Transplantation	RCV000003928	SCV000540756	pathogenic	Familial hypercholesterolemia 1	2016-11-05	criteria provided, single submitter	clinical testing
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille	RCV000003928	SCV000583728	pathogenic	Familial hypercholesterolemia 1	2017-03-30	criteria provided, single submitter	clinical testing
Laboratory of Genetics and Molecular Cardiology, University of São Paulo	RCV000003928	SCV000588513	pathogenic	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	research
Color Health, Inc	RCV000775046	SCV000909144	pathogenic	Familial hypercholesterolemia	2018-06-18	criteria provided, single submitter	clinical testing	Pathogenic variant based on current evidence: This variant is a single nucleotide substitution in exon 4 of the LDLR gene, which creates a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional assays have not been performed for this variant. While this variant is rare in the general population (0/277264 chromosomes in the Genome Aggregation Database (gnomAD)), it has been reported in multiple individuals affected with familial hypercholesterolemia (PMID: 8093663, 16389549, 22883975). Truncating variants in LDLR are known to be pathogenic (PMID: 20809525). Based on available evidence, this variant is classified as Pathogenic.
Invitae	RCV000775046	SCV000952013	pathogenic	Familial hypercholesterolemia	2018-08-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Cys231*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in many individuals affected with familial hypercholesterolemia (PMID: 8093663, 22698793, 27680772, 16389549, 22883975, 20145306, 21310417, 10559517). This variant is also known as Cys210X in the literature. ClinVar contains an entry for this variant (Variation ID: 3730). Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000003928	SCV000024093	pathogenic	Familial hypercholesterolemia 1	1993-01-01	no assertion criteria provided	literature only
Cardiovascular Genetics Laboratory,PathWest Laboratory Medicine WA - Fiona Stanley Hospital	RCV000003928	SCV000268583	pathogenic	Familial hypercholesterolemia 1	2008-07-09	no assertion criteria provided	clinical testing