Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004992087 | SCV005609304 | pathogenic | Cardiovascular phenotype | 2024-10-05 | criteria provided, single submitter | clinical testing | The c.648dupT pathogenic mutation, located in coding exon 4 of the LDLR gene, results from a duplication of T at nucleotide position 648, causing a translational frameshift with a predicted alternate stop codon (p.D217*). This variant has been reported in association with familial hypercholesterolemia (FH) (Defesche JC et al. J Clin Lipidol, 2017 Sep;11:1338-1346.e7; Guardamagna O et al. J Pediatr, 2009 Aug;155:199-204.e2; Di Taranto MD et al. Clin Genet, 2021 Nov;100:529-541). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
| Laboratory of molecular diagnosis of dyslipidemias, |
RCV000211601 | SCV001653605 | pathogenic | Hypercholesterolemia, familial, 1 | 2021-05-24 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001389664 | SCV001591109 | pathogenic | Familial hypercholesterolemia | 2023-07-14 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with hypercholesterolemia (PMID: 19446849). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asp217*) 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). ClinVar contains an entry for this variant (Variation ID: 226328). For these reasons, this variant has been classified as Pathogenic. |
| Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV001256904 | SCV001433409 | pathogenic | not provided | 2019-02-26 | criteria provided, single submitter | clinical testing | |
| U4M - |
RCV000211601 | SCV000583713 | pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
| Robarts Research Institute, |
RCV000211601 | SCV000484804 | likely pathogenic | Hypercholesterolemia, familial, 1 | criteria provided, single submitter | clinical testing | ||
| LDLR- |
RCV000211601 | SCV000294849 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Cardiovascular Genetics Laboratory, |
RCV000211601 | SCV000268573 | pathogenic | Hypercholesterolemia, familial, 1 | 2014-08-14 | no assertion criteria provided | clinical testing |