Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000238083 | SCV004022421 | uncertain significance | Hypercholesterolemia, familial, 1 | 2023-04-28 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.914G>C (p.Trp305Ser) variant is classified as Uncertain significance - insufficient evidence for Familial Hypercholesterolemia by applying evidence codes PS4_Supporting, PM2, PP1, and PP4 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: PS4_Supporting: Variant meets PM2 and is identified in 2 index cases with DLCN criteria of probable FH from Lille University & CHRU Lille. So, PS4_Supporting is met. PM2: This variant is absent from gnomAD (gnomAD v2.1.1). So, PM2 is met. PP1: Variant segregates with FH phenotype in 2 informative meioses in 1 families from Centre de Génétique Moléculaire et Chromosomique, Unité de génétique de l'Obésité et des Dyslipidémies. So, PP1 is met. PP4: Variant meets PM2 and is identified in 2 index cases who fulfill clinical criteria for FH, after alternative causes of high cholesterol were excluded (see PS4 for details). |
LDLR- |
RCV000238083 | SCV000295049 | uncertain significance | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000238083 | SCV000503252 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 , family members = 2 with co-segregation / previously described in association with FH |
U4M - |
RCV000238083 | SCV000583760 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing |