Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000211626 | SCV000295581 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Cardiovascular Research Group, |
RCV000211626 | SCV000322969 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | 0/208 non-FH alleles; 0/100 control subjects |
Robarts Research Institute, |
RCV000211626 | SCV000484725 | likely pathogenic | Familial hypercholesterolemia 1 | criteria provided, single submitter | clinical testing | ||
Centre de Génétique Moléculaire et Chromosomique, |
RCV000211626 | SCV000503384 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 8 , family member = 1 with co-segregation / systematically associated with c.2397_2405del, p.Val800_Leu802del & other mutations at same codon / Software predictions: Damaging |
Laboratory of Genetics and Molecular Cardiology, |
RCV000211626 | SCV000588602 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Fundacion Hipercolesterolemia Familiar | RCV000211626 | SCV000607623 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Iberoamerican FH Network | RCV000211626 | SCV000748058 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | |
Invitae | RCV001034619 | SCV000820242 | uncertain significance | Familial hypercholesterolemia | 2019-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with histidine at codon 564 of the LDLR protein (p.Asn564His). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with hypercholesterolemia (PMID: 7550239, 17765246, 23054246) including many in whom it has been shown to coincide on the same chromosome (in cis) with p.Val800_Leu802del (PMID: 9147888, 9143924, 12442279, 10090484). However, presence of p.Val800_Leu802del can not be excluded from the individuals for whom only this single c.1690A>C variant was reported. This variant is also known as N543H in the literature. ClinVar contains entries for this variant (Variation ID: 3737, 226365). Experimental studies have shown that this variant has a mild impact on LDLR protein function. However, when expressed with p.Val800_Leu802del in the same cDNA, LDLR receptor function was greatly reduced (PMID: 9143924). A different missense substitution at this codon (p.Asn564Ser) has been determined to be pathogenic (PMID: 9654205, 21376320 20145306, 20538126). This suggests that the asparagine residue is critical for LDLR protein function and that other missense substitutions at this position may also be pathogenic. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Brunham Lab, |
RCV000211626 | SCV001432662 | likely pathogenic | Familial hypercholesterolemia 1 | 2019-01-27 | criteria provided, single submitter | research | |
Cardiovascular Genetics Laboratory, |
RCV000211626 | SCV000268628 | pathogenic | Familial hypercholesterolemia 1 | 2012-08-01 | no assertion criteria provided | clinical testing | |
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000211626 | SCV000606484 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research | ||
Diagnostic Laboratory, |
RCV000211626 | SCV000733825 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | clinical testing |