Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237494 | SCV000295919 | pathogenic | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Robarts Research Institute, |
RCV000237494 | SCV000484732 | likely pathogenic | Familial hypercholesterolemia 1 | criteria provided, single submitter | clinical testing | ||
| Centre de Génétique Moléculaire et Chromosomique, |
RCV000237494 | SCV000503474 | uncertain significance | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1/FH-Japan |
| Invitae | RCV000791393 | SCV000544653 | pathogenic | Familial hypercholesterolemia | 2018-11-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal at codon 739 (p.Gln739*) of 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. This particular variant has been reported in the literature in individuals with familial hypercholesterolemia (PMID: 12417285, 20045108, 20538126, 21376320, 23375686). This variant is also known as p.Gln718X in the literature. For these reasons, this variant has been classified as Pathogenic. |
| Color | RCV000791393 | SCV001356940 | pathogenic | Familial hypercholesterolemia | 2018-12-14 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000791393 | SCV001361871 | pathogenic | Familial hypercholesterolemia | 2019-10-29 | criteria provided, single submitter | clinical testing | Variant summary: LDLR c.2215C>T (p.Gln739X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251316 control chromosomes (gnomAD). c.2215C>T has been reported in the literature in multiple individuals affected with Familial Hypercholesterolemia (Yu_2002, Robles-Osorio_2006, Romano_2010, Chiou_2010, Pirillo_2017, Kolansky_2008). These data indicate that the variant is very likely to be associated with disease. At least one publication reported that the variant resulted in less than 2% of normal LDLR activity in patient derived skin fibroblasts (Kolansky_2008). Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (2x) and as VUS (1x). Based on the evidence outlined above, the variant was classified as pathogenic. |