Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000498619 | SCV000590083 | pathogenic | not provided | 2018-08-08 | criteria provided, single submitter | clinical testing | The E514X variant in the LDLR gene has not been reported as a pathogenic or benign to our knowledge. This variant is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the LDLR gene have been reported in Human Gene Mutation Database in association with FH (Stenson et al., 2014). Furthermore, the E514X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). |
Labcorp Genetics |
RCV001851374 | SCV002125157 | pathogenic | Familial hypercholesterolemia | 2022-03-29 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with LDLR-related conditions. 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 create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 432366). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu514*) 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). |