Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000003885 | SCV000295551 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000003885 | SCV000503379 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 6 , family members = 8 with co-segregation / FH-Saint-Omer, < 2% LDLR Activity / Software predictions: Damaging |
U4M - |
RCV000003885 | SCV000583857 | pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Laboratory of Genetics and Molecular Cardiology, |
RCV000003885 | SCV000588599 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Integrated Genetics/Laboratory Corporation of America | RCV001175478 | SCV001339064 | pathogenic | Familial hypercholesterolemia | 2020-03-16 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.1637G>A (p.Gly546Asp) results in a non-conservative amino acid change located in one of the class B repeats (IPR000033) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251462 control chromosomes (gnomAD). The variant c.1637G>A (also known as FH Saint Omer and G525D) has been reported in the literature in multiple individuals (including at least one homozygote) who were affected with Familial Hypercholesterolemia (e.g. Hobbs_1992, Klancar_2015, Martin-Campos_2018). These data indicate that the variant is very likely to be associated with disease. Publications also reported experimental evidence evaluating an impact on protein function, and demonstrated that the variant causes the retention of the protein in the endoplasmic reticulum, with eventual ubiquitination and degradation, predicted to result in the complete lack of the LDL receptor at the cell surface (Hobbs_1990, Zelcer_2009). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic (2x) / likely pathogenic (2x). Based on the evidence outlined above, the variant was classified as pathogenic. |
Centre for Mendelian Genomics, |
RCV000003885 | SCV001370229 | pathogenic | Familial hypercholesterolemia 1 | 2019-04-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PS3,PM2,PP3,PP4. |
Brunham Lab, |
RCV000003885 | SCV001432661 | pathogenic | Familial hypercholesterolemia 1 | 2019-05-11 | criteria provided, single submitter | research | |
OMIM | RCV000003885 | SCV000024050 | pathogenic | Familial hypercholesterolemia 1 | 1988-11-01 | no assertion criteria provided | literature only | |
Cardiovascular Genetics Laboratory, |
RCV000003885 | SCV000268626 | pathogenic | Familial hypercholesterolemia 1 | 2011-10-17 | no assertion criteria provided | clinical testing | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000003885 | SCV000606473 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research |