Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000508899 | SCV002506343 | uncertain significance | Hypercholesterolemia, familial, 1 | 2021-12-13 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.259T>C (p.Trp87Arg) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes (PM2, PM5 and PP3) 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), so PM2 is met. PM5 - 1 other missense variant in the same codon: - NM_000527.5(LDLR):c.259T>G (p.Trp87Gly) - Pathogenic by expert panel in ClinVar, so PM5 is met. PP3 - REVEL = 0.891. It is above 0.75, so PP3 is met. |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000508899 | SCV000606050 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |