Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV000237881 | SCV004022467 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2023-04-28 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.299A>G (p.Asp100Gly) variant is classified as likely pathogenic for Familial Hypercholesterolemia by applying evidence codes PM2, PP1, PP3, PP4, PS4_supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1016/j.gim.2021.09.012). The supporting evidence is as follows: - PM2: This variant is absent from gnomAD (gnomAD v2.1.1). - PP1: variant segregates with FH phenotype in 3 informative meiosis in 1 family from Laboratory of Genetics and Molecular Cardiology: 2 relatives with the phenotype and the variant and 1 relative without the phenotype and without the variant. - PP3: REVEL = 0.9. - PP4: Variant meets PM2 and is identified in at least 1 index case (1 index case from Laboratory of Genetics and Molecular Cardiology with Simon-Broome criteria of possible FH, 1 index case from PMID: 11810272 clinically diagnosed with definite heterozygous FH), after alternative causes of high cholesterol were excluded. - PS4_supporting: Variant meets PM2 and is identified in 2 index cases (1 index case from Laboratory of Genetics and Molecular Cardiology with Simon-Broome criteria of possible FH, 1 index case from PMID: 11810272 clinically diagnosed with definite heterozygous FH) |
| LDLR- |
RCV000237881 | SCV000294588 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237881 | SCV000606067 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |