Submissions for variant NM_000527.5(LDLR):c.564C>G (p.Tyr188Ter) (rs121908034)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
LDLR-LOVD, British Heart Foundation	RCV000003925	SCV000294795	pathogenic	Familial hypercholesterolemia 1	2016-03-25	criteria provided, single submitter	literature only
Robarts Research Institute,Western University	RCV000003925	SCV000484764	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	RCV000003925	SCV000503182	pathogenic	Familial hypercholesterolemia 1	2016-12-16	criteria provided, single submitter	clinical testing	subject mutated among 2600 FH index cases screened = 1/previously described in association with FH
Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000003925	SCV000599335	pathogenic	Familial hypercholesterolemia 1	2016-03-01	criteria provided, single submitter	curation
Invitae	RCV001186871	SCV000627042	pathogenic	Familial hypercholesterolemia	2019-10-31	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr188*) 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 reported to segregate with familial hypercholesterolemia in a single family (PMID: 1734722) and has been observed in several individuals with familial hypercholesterolemia (PMID: 8882879). This variant is also known as p.Tyr167* in the literature. ClinVar contains an entry for this variant (Variation ID: 3727). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). For these reasons, this variant has been classified as Pathogenic.
Color	RCV001186871	SCV001353461	pathogenic	Familial hypercholesterolemia	2018-11-21	criteria provided, single submitter	clinical testing
OMIM	RCV000003925	SCV000024090	pathogenic	Familial hypercholesterolemia 1	1992-02-01	no assertion criteria provided	literature only
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde,Academisch Medisch Centrum	RCV000003925	SCV000606160	pathogenic	Familial hypercholesterolemia 1		no assertion criteria provided	research