Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000237679 | SCV002506336 | uncertain significance | Hypercholesterolemia, familial, 1 | 2021-12-16 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.1223A>C (p.Glu408Ala) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PM2, PP3, PP4 and PS4_Supporting as defined by the ClinGen Familial Hypercholesterolemia Expert Panel LDLR-specific variant curation guidelines (https://doi.org/10.1101/2021.03.17.21252755). The supporting evidence is as follows: PM2 - This variant was not identified in gnomAD (gnomAD v2.1.1), so PM2 is met. PP3 - REVEL = 0.914. It is above 0.75, so PP3 is met. PP4 - variant meets PM2 and was identified in at least 1 index case with DLCN score of probable FH from U4M - Lille University & CHRU Lille, Université de Lille - CHRU de Lille (SCV000583810.1), France, so PP4 is met. PS4_supporting - variant meets PM2 and was identified in 2 unrelated index cases with SB criteria for FH (total and LDL-cholesterol levels above the 95th percentile of a sex and age-matched French population and autosomal dominant transmission of hypercholesterolemia in the family) from PMID 20809525 (Marduel et al., 2010), France, so PS4_Supporting is met |
LDLR- |
RCV000237679 | SCV000295309 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
U4M - |
RCV000237679 | SCV000583810 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing |