Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237143 | SCV000295721 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Invitae | RCV000775248 | SCV000544648 | pathogenic | Familial hypercholesterolemia | 2022-12-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp620*) in the LDLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LDLR are known to be pathogenic (PMID: 20809525, 28645073). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 252089). This premature translational stop signal has been observed in individuals with familial hypercholesterolemia (PMID: 20809525, 25846081). This variant is not present in population databases (gnomAD no frequency). |
U4M - |
RCV000237143 | SCV000583899 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Human Genome Sequencing Center Clinical Lab, |
RCV000237143 | SCV000839977 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-05-17 | criteria provided, single submitter | clinical testing | The c.1860G>A (p.Trp620*) variant in the LDLR gene has been reported in one patient with autosomal dominant hypercholesterolemia [PMID 20809525]. This variant also segregated with the phenotype within the reported proband’s family. The c.1860G>A change creates a premature stop codon at amino acid position 620 of the LDLR protein and is thus predicted to result in a loss of function of the protein. The c.1860G>A change has not been reported in the ExAC database. Another nucleotide change (c.1859G>A) similarly resulting a non sense variant at the same amino acid position 620 (p.Trp620*) has also been reported in patients with hypercholesterolemia [PMID 11737238]. This c.1860G>A (p.Trp620*) variant is thus classified as pathogenic. |
Color Diagnostics, |
RCV000775248 | SCV000909506 | pathogenic | Familial hypercholesterolemia | 2023-09-01 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 13 in the LDLR type B repeat 6 of the LDLR gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in at least two individuals affected with familial hypercholesterolemia (PMID: 20809525, 25846081, 28235710) and in one individual suspected to be affected with familial hypercholesterolemia (PMID: 34037665). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of LDLR function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Ambry Genetics | RCV002411099 | SCV002724100 | pathogenic | Cardiovascular phenotype | 2022-01-24 | criteria provided, single submitter | clinical testing | The p.W620* pathogenic mutation (also known as c.1860G>A), located in coding exon 13 of the LDLR gene, results from a G to A substitution at nucleotide position 1860. This changes the amino acid from a tryptophan to a stop codon within coding exon 13. This variant has been reported in individuals with familial hypercholesterolemia (FH), segregating with disease in two families (Marduel M et al. Hum Mutat, 2010 Nov;31:E1811-24; Fan LL et al. Appl Biochem Biotechnol, 2015 May;176:101-9; Xiang R et al. Atherosclerosis, 2017 03;258:84-88; Sturm AC et al. JAMA Cardiol, 2021 08;6:902-909). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Fulgent Genetics, |
RCV000237143 | SCV002813234 | pathogenic | Hypercholesterolemia, familial, 1 | 2021-09-20 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV003480570 | SCV004227681 | pathogenic | not provided | 2022-09-26 | criteria provided, single submitter | clinical testing | PP1, PM2_supporting, PVS1 |