Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237262 | SCV000294785 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237262 | SCV000503179 | likely benign | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 / Software predictions: Conflicting |
Molecular Genetics Laboratory, |
RCV000237262 | SCV000540742 | uncertain significance | Familial hypercholesterolemia 1 | 2016-11-05 | criteria provided, single submitter | clinical testing | |
U4M - |
RCV000237262 | SCV000583701 | likely pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000161959 | SCV000697237 | uncertain significance | not provided | 2016-03-15 | criteria provided, single submitter | clinical testing | Variant summary: The c.542C>G affects a non-conserved nucleotide, resulting in an amino acid change, Pro to Arg. 3/4 in-silico tools (SNPs&GO not captured here due to low reliability index) predict this variant to be damaging. This variant was found in 7/131378 control chromosomes including the broad and large populations of ExAC at a frequency of 0.0000533, which does not exceed the predicted maximum expected allele frequency for a pathogenic LDLR variant (0.0012508). This variant has been reported in many FH patients/families with both co-segregation of variant with disease as well as lack of co-segregation observed (Garcia-Garcia_ 2001 and Garcia-Garcia _2011). In vitro functional studies showed that variant of interest altered LDLR precursor processing to the mature form, however, the protein activity was normal (Garcia-Garcia _2011) and showed comparable levels of cellular LDL-uptake to wild type (Thormaehlen_2015), suggesting a possible lack of functional effect which needs to be further clarified. Considering all, there is not enough evidence to conclude on either the pathogenicity or neutral effect of this variant. Therefore, this variant has been classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
Human Genome Sequencing Center Clinical Lab, |
RCV000237262 | SCV000839992 | likely pathogenic | Familial hypercholesterolemia 1 | 2018-04-25 | criteria provided, single submitter | clinical testing | This c.542C>G (p.Pro181Arg) variant in the LDLR gene has been reported in multiple familial hypercholesterolaemia patients [PMID: 11600564, 11754108, 16250003, 23375686] than that observed as extremely low in general population according to gnomad database. Functional studies showed impairment of precursor LDLR with reduced penetrance associated with this variant [PMID: 21868016]. Multiple in silico predictions suggest this proline to arginine is deleterious. Based upon above evidences, c.542C>G (p.Pro181Arg) variant in the LDLR gene is classified as likely pathogenic. |
Color | RCV001181335 | SCV001346460 | uncertain significance | Familial hypercholesterolemia | 2020-03-12 | criteria provided, single submitter | clinical testing | |
Dept. |
RCV000161959 | SCV000189534 | not provided | not provided | no assertion provided | in vitro | ||
Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237262 | SCV000606153 | pathogenic | Familial hypercholesterolemia 1 | no assertion criteria provided | research | ||
Natera, |
RCV001181335 | SCV001456144 | uncertain significance | Familial hypercholesterolemia | 2020-09-16 | no assertion criteria provided | clinical testing |