Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000238264 | SCV005688655 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2025-01-31 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.1328G>C (p.Trp443Ser) variant is classified as Likely Pathogenic for Familial Hypercholesterolemia by applying ACMG/AMP evidence codes PM2, PM5, PS4_Moderate, PP3 and PP4 as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (specification version 1.2) on 31 January 2025. The supporting evidence is as follows: PM2: PopMax MAF = 0.0000006841 (0.00006841 %) in European (non-Finnish) exomes (gnomAD version 4.1.0). PP3: REVEL = 0.934. PM5: 1 other missense variant in the same codon: NM_000527.5(LDLR):c.1329G>C (p.Trp443Cys) (ClinVar ID 251792)- Pathogenic by these guidelines. PS4_Moderate, PP4: Variant meets PM2 and is identified in at least 9 unrelated index cases who fulfill criteria for FH: 1 case meeting Simon Broome criteria from PMID 17142622 (Humphries et al., 2006), UK; 1 case meeting Simon Broome possible FH criteria from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies, APHP.Sorbonne Université, Hôpital de la Pitié-Salpêtrière, France; 3 cases with DLCN >=6 from U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille, France; 4 cases with DLCN >=6 from PMID 34871818 (Tada et al., 2022), Japan. |
LDLR- |
RCV000238264 | SCV000295369 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000238264 | SCV000503333 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 / previously described in association with FH / Software predictions: Damaging |
U4M - |
RCV000238264 | SCV000583821 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Fundacion Hipercolesterolemia Familiar | RCV000238264 | SCV000607586 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-03-01 | criteria provided, single submitter | research | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000238264 | SCV000606395 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |