Submissions for variant NM_000527.4(LDLR):c.2479G>T (p.Val827Phe) (rs137853964)

Total submissions: 2

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	RCV000417325	SCV000503494	likely 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/Software predictions: Conflicting
Broad Institute Rare Disease Group,Broad Institute	RCV001248957	SCV001422751	uncertain significance	Familial hypercholesterolemia	2020-01-22	no assertion criteria provided	curation	The p.Val827Phe variant in LDLR has been reported in 2 Moroccan individuals with familial hypercholesterolemia (PMID: 30415195), and was absent from large population studies. This variant has also been reported in ClinVar as likely pathogenic (Variation ID: 375840). Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, PS4_supporting (Richards 2015).