ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.1433G>A (p.Gly478Glu)

dbSNP: rs1555805380
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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 RCV000508770 SCV002506345 likely pathogenic Hypercholesterolemia, familial, 1 2022-01-31 reviewed by expert panel curation The NM_000527.4(LDLR):c.1433G>A (p.Gly478Glu) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes PM2, PM5, PP3 and PP4 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), so PM2 is met. PM5 - 2 other missense variants in the same codon: (1) NM_000527.5(LDLR):c.1432G>A (p.Gly478Arg) - 1 star, Conflicting interpretations of pathogenicity: Likely pathogenic(8);Pathogenic(1);Uncertain significance(4) - Pathogenic by these guidelines (FH VCEP training Aug 2021) (2) NM_000527.5(LDLR):c.1432G>T (p.Gly478Trp) - 1 star, VUS in ClinVar - VUS by these guidelines --- there is 1 Pathogenic variant in the same codon, so PM5 is met. PP3 - REVEL = 0.984. It is above 0.75, so PP3 is met. PP4 - variant meets PM2 and was identified in 1 index case who fulfills Simon-Broome criteria from Cardiovascular Research Group,Instituto Nacional de Saude Doutor Ricardo Jorge, so PP4 is met
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000508770 SCV000606424 pathogenic Hypercholesterolemia, familial, 1 no assertion criteria provided research

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