ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1153C>G (p.Leu385Val)

gnomAD frequency: 0.00001  dbSNP: rs879254808
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000237369 SCV004022440 uncertain significance Hypercholesterolemia, familial, 1 2023-04-28 reviewed by expert panel curation The NM_000527.5(LDLR):c.1153C>G (p.Leu385Val) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PP4 and BP4) as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines ( The supporting evidence is as follows: PM2: This variant is absent from gnomAD (gnomAD v2.1.1). PP4: Variant meet PM2. PMID: 20809525 (Marduel et al., 2010), France - 1 case who fulfills Simon-Broome criteria for FH. BP4: REVEL = 0.432. It is below 0.50, so splicing evaluation is required. Functional data on splicing not available. A) not on limits B) it creates a GT score in MES: de novo donor = 3.09, authentic donor = 7.23. Ratio de novo/authentic is 0.43. It is below 0.8. C) not on limits Variant is not predicted to alter splicing.
LDLR-LOVD, British Heart Foundation RCV000237369 SCV000295248 likely benign Hypercholesterolemia, familial, 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 RCV000237369 SCV000503305 likely pathogenic Hypercholesterolemia, familial, 1 2016-12-16 criteria provided, single submitter clinical testing subject mutated among 2600 FH index cases screened = 1 / Software predictions: Benign
GeneDx RCV003441824 SCV004168105 uncertain significance not provided 2023-10-25 criteria provided, single submitter clinical testing Identified in an individual with hypercholesterolemia, however, detailed clinical and segregation information were not provided (PMID: 20809525); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 20809525)

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