Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
SNPedia | RCV000210844 | SCV000267120 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-04-03 | criteria provided, single submitter | literature only | |
LDLR- |
RCV000210844 | SCV000295890 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000210844 | SCV000503468 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 5 , family members = 5 |
U4M - |
RCV000210844 | SCV000583930 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000523095 | SCV000617496 | pathogenic | not provided | 2021-04-14 | criteria provided, single submitter | clinical testing | Identified in at least two unrelated patients with familial hypercholesterolemia (FH) in the published literature (also reported as E693X due to alternate nomenclature) (Amsellam et al., 2002; Khera et al., 2016), and in a patient referred for testing at GeneDx.; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Reported in ClinVar as pathogenic (ClinVar Variant ID#225183; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 27050191, 12436241, 25525159, 12124988) |
Invitae | RCV002229190 | SCV000752420 | pathogenic | Familial hypercholesterolemia | 2023-02-14 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 225183). This variant is also known as E693X. This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 12124988, 12436241). This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Glu714*) 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). |
Ambry Genetics | RCV002426986 | SCV002730086 | pathogenic | Cardiovascular phenotype | 2021-05-27 | criteria provided, single submitter | clinical testing | The p.E714* pathogenic mutation (also known as c.2140G>T), located in coding exon 14 of the LDLR gene, results from a G to T substitution at nucleotide position 2140. This changes the amino acid from a glutamic acid to a stop codon within coding exon 14. This alteration, which is also known as p.E693*, has been reported in familial hypercholesterolemia (FH) cohorts (Amsellem S et al. Hum Genet, 2002 Dec;111:501-1; Khera AV et al. J Am Coll Cardiol, 2016 06;67:2578-89; Marmontel O et al. Clin Genet, 2018 07;94:132-140). In addition to the clinical data presented in the literature, 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. |