ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.2037T>A (p.Tyr679Ter) (rs760436036)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
LDLR-LOVD, British Heart Foundation RCV000238543 SCV000295832 pathogenic Familial hypercholesterolemia 1 2016-03-25 criteria provided, single submitter literature only
Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies,APHP, GH Hôpitaux Universitaires Pitié-Salpêtrière / Charles-Foix RCV000238543 SCV000503451 pathogenic Familial hypercholesterolemia 1 2016-12-16 criteria provided, single submitter clinical testing subjects mutated among 2600 FH index cases screened = 7 , family members = 4 with co-segregation
Broad Institute Rare Disease Group, Broad Institute RCV001248907 SCV001422600 likely pathogenic Familial hypercholesterolemia 2020-01-22 no assertion criteria provided curation The p.Tyr679Ter variant in LDLR has been reported in one individual from the UK with familial hypercholesterolemia (PMID: 17539906), and was absent from large population studies. This variant has also been reported in ClinVar as pathogenic (Variation ID: 252183). This nonsense variant leads to a premature termination codon at position 679, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the LDLR gene is an established disease mechanism in familial hypercholesterolemia. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).

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