Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000237727 | SCV002506349 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2022-02-01 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.1784G>T (p.Arg595Leu) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM2, PP3, PM5_strong) 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. PP3 - REVEL = 0.959. It is above 0.75, so PP3 is Met. PM5_strong - 2 other missense variants in the same codon: - NM_000527.5(LDLR):c.1783C>T (p.Arg595Trp) (ClinVar ID: 161290) - Pathogenic by these guidelines - NM_000527.5(LDLR):c.1784G>A (p.Arg595Gln) (ClinVar ID: 183126) - Pathogenic by these guidelines There are 2 variants in the same codon classified as Pathogenic by these guidelines, so PM5_Strong is Met. |
LDLR- |
RCV000237727 | SCV000295656 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237727 | SCV000606514 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |