Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999375 | SCV005625805 | pathogenic | not provided | 2024-10-21 | criteria provided, single submitter | clinical testing | The LDLR c.1187del (p.Gly396Alafs*17) variant alters the translational reading frame of the LDLR mRNA and causes the premature termination of LDLR protein synthesis. In the published literature, this variant has been reported in individual(s) with a personal and/or family history of familial hypercholesterolemia (PMIDs: 34297352 (2021), 30710474 (2019)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic. |
| Labcorp Genetics |
RCV003581655 | SCV004272270 | pathogenic | Familial hypercholesterolemia | 2023-06-17 | 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: 375810). This premature translational stop signal has been observed in individual(s) with familial hypercholesterolemia (PMID: 30710474). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gly396Alafs*17) 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). |
| 3billion | RCV000417253 | SCV002572880 | pathogenic | Hypercholesterolemia, familial, 1 | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. The variant in the canonical splice site is predicted to alter splicing, resulting in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000375810). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |
| Laboratory of molecular diagnosis of dyslipidemias, |
RCV000417253 | SCV001653625 | pathogenic | Hypercholesterolemia, familial, 1 | 2021-05-24 | criteria provided, single submitter | clinical testing | |
| Centre de Génétique Moléculaire et Chromosomique, |
RCV000417253 | SCV000503312 | pathogenic | Hypercholesterolemia, familial, 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000417253 | SCV000606349 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |