Submissions for variant NM_000527.4(LDLR):c.1978C>T (p.Gln660Ter) (rs193922569)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Integrated Genetics/Laboratory Corporation of America	RCV000030130	SCV000052785	likely pathogenic	Familial hypercholesterolemia 1	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Likely pathogenic.
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix	RCV000030130	SCV000503445	pathogenic	Familial hypercholesterolemia 1	2016-12-16	criteria provided, single submitter	clinical testing	subject mutated among 2600 FH index cases screened = 1
GeneDx	RCV000498572	SCV000589576	pathogenic	not provided	2017-06-02	criteria provided, single submitter	clinical testing	The Q660X variant in the LDLR gene has been reported previously as Q639X (due to alternate nomenclature) in one Flemish individual with FH (Varret et al., 1998). The Q660X variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the LDLR gene have been reported in the Human Gene Mutation Database in association with FH, and loss-of-function is an established mechanism of disease in the LDLR gene (Stenson et al., 2014). Furthermore, the Q660X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).