ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1367T>A (p.Leu456His)

dbSNP: rs200143634
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000237859 SCV005375303 uncertain significance Hypercholesterolemia, familial, 1 2023-06-23 reviewed by expert panel curation The NM_000527.5 (LDLR):c.1367T>A (p.Leu456His) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP3, PP4 and PP1 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 23 June 2023. The supporting evidence is as follows: PM2: Variant is absent from gnomAD (gnomAD v2.1.1). PP3: REVEL=0.856. PP4: Variant meets PM2 and is identified in 1 index case who fulfills criteria for FH after alternative causes of high cholesterol were excluded (PMID 16542394, Brusgaard et al., 2006, Denmark). PP1: Variant segregates with FH phenotype in at least 2 informative meioses from 1 family (PMID 16542394, Brusgaard et al., 2006, Denmark): 2 affected family members have the variant.
LDLR-LOVD, British Heart Foundation RCV000237859 SCV000295399 likely pathogenic Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only

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