ClinVar Miner

Submissions for variant NM_000527.5(LDLR):c.-13A>G

gnomAD frequency: 0.00001  dbSNP: rs376011618
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Familial Hypercholesterolemia Variant Curation Expert Panel RCV000237905 SCV005903151 uncertain significance Hypercholesterolemia, familial, 1 2024-10-28 reviewed by expert panel curation The NM_000527.5(LDLR):c.-13A>G variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PP4, and BS3_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on October 28th, 2024. The supporting evidence is as follows: PM2: PopMax MAF = 0.00002374 (0.0023%) in European (Non-Finnish) exomes+genomes (gnomAD v4.1.0). BS3_Supporting: Level 3 assays - PMID 25248394 (Khamis et al., 2015): Heterologous cells (Huh7), Luciferase assays: results - normal (96%) gene expression. PMID 31395865 (Kircher et al., 2019): Heterologous cells (HepG2), luciferase assays: results - 97-106% gene expression. So, BS3_Supporting is met. PP4: Variant meets PM2 and is identified in 1 case meeting Simon Broome criteria from the Cardiovascular Research Group, Instituto Nacional de Saúde Doutor Ricardo Jorge, Portugal, after alternative causes of high cholesterol were excluded.
LDLR-LOVD, British Heart Foundation RCV000237905 SCV000294403 likely benign Hypercholesterolemia, familial, 1 2016-03-25 criteria provided, single submitter literature only
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge RCV000237905 SCV000322869 benign Hypercholesterolemia, familial, 1 2016-03-01 criteria provided, single submitter research 0/190 non-FH alleles
Color Diagnostics, LLC DBA Color Health RCV001186035 SCV001352365 likely benign Familial hypercholesterolemia 2017-09-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001186035 SCV002322565 likely benign Familial hypercholesterolemia 2023-08-30 criteria provided, single submitter clinical testing
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, Academisch Medisch Centrum RCV000237905 SCV000605989 uncertain significance Hypercholesterolemia, familial, 1 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV003947809 SCV004758487 likely benign LDLR-related disorder 2019-12-27 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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