ClinVar Miner

Submissions for variant NM_000527.4(LDLR):c.1730G>A (p.Trp577Ter) (rs138947766)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000417240 SCV000503401 pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 5 , family members = 4 with co-segregation / Other nonsens mutation at same codon with < 2% LDLR Activity
U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille RCV000417240 SCV000583871 pathogenic Familial hypercholesterolemia 1 2017-03-30 criteria provided, single submitter clinical testing
Fundacion Hipercolesterolemia Familiar RCV000417240 SCV000607633 pathogenic Familial hypercholesterolemia 1 2016-03-01 criteria provided, single submitter research
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996757 SCV001151666 likely pathogenic not provided 2019-06-01 criteria provided, single submitter clinical testing
Invitae RCV001049063 SCV001213097 pathogenic Familial hypercholesterolemia 2019-01-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp577*) 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 several individuals affected with familial hypercholesterolemia (PMID: 23680767, 24507775, 26802169). ClinVar contains an entry for this variant (Variation ID: 375821). A different variant (c.1731G>A) giving rise to the same protein effect observed here (p.Trp577*) has been determined to be pathogenic (PMID: 1301956, Invitae). This suggests that this variant is also likely to be causative of disease. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525). For these reasons, this variant has been classified as Pathogenic.

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