Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000495884 | SCV004022388 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2023-03-20 | reviewed by expert panel | curation | The NM_000527.5(LDLR):c.551G>C (p.Cys184Ser) variant is classified as Likely pathogenic for Familial Hypercholesterolemia by applying evidence codes (PM1, PM2, PP3, 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: PM1 - Variant meets PM2 and alters Cys184, one of the cysteine residues listed. PM2 - This variant is absent from gnomAD (gnomAD v2.1.1). PP3 - REVEL = 0.871. It is above 0.75. PP4 - Variant meets PM2 and is identified in 1 index case who fulfills DLCN>=6 criteria for FH from Service de Biochimie et de Biologie Moléculaire, Hospices Civils de Lyon, Lyon, France, after alternative causes for high cholesterol were excluded. |
U4M - |
RCV000495884 | SCV000583703 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588844 | SCV000697239 | uncertain significance | not provided | 2016-11-22 | criteria provided, single submitter | clinical testing | Variant summary: The LDLR c.551G>C (p.Cys184Ser) variant involves the alteration of a conserved nucleotide. This variant is located in the Low-density lipoprotein (LDL) receptor class A repeat domain (InterPro). Although the substitution does not exhibit a shift in polarity, 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 121044 control chromosomes. One database lists this variant in an individual without clinical information. Other variants affecting the same amino acids, p.Cys184Arg, p.Cys184Tyr, p.Cys184Trp, have been clssified as pathogenic/likely pathogenic in ClinVar. Taken together, this variant is classified as VUS-possibly pathogenic. |