Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
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- |
RCV000237905 | SCV000294403 | likely benign | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Cardiovascular Research Group, |
RCV000237905 | SCV000322869 | benign | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | 0/190 non-FH alleles |
Color Diagnostics, |
RCV001186035 | SCV001352365 | likely benign | Familial hypercholesterolemia | 2017-09-18 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001186035 | SCV002322565 | likely benign | Familial hypercholesterolemia | 2023-08-30 | criteria provided, single submitter | clinical testing | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237905 | SCV000605989 | uncertain significance | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research | ||
Prevention |
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). |