Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
U4M - |
RCV000495862 | SCV000583937 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Broad Center for Mendelian Genomics, |
RCV000495862 | SCV001423094 | uncertain significance | Hypercholesterolemia, familial, 1 | 2020-01-22 | criteria provided, single submitter | curation | The p.Gly754Trp variant in LDLR has been reported in two individuals with probable Familial Hypercholesterolemia in ClinVar (Variation ID: 430797), and has been identified in 0.002891% (1/34588) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs559239150). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. This variant has also been reported likely pathogenic in ClinVar (Variation ID: 430797). In summary, the clinical significance of the p.Gly754Trp variant is uncertain. ACMG/AMP Criteria applied: none (Richards 2015). |
All of Us Research Program, |
RCV000495862 | SCV004829387 | uncertain significance | Hypercholesterolemia, familial, 1 | 2023-05-16 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Gly733Trp in the mature protein) replaces glycine with tryptophan at codon 754 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with hypercholesterolemia and hyperbetalipoproteinemia (ClinVar SCV000583937.1). This variant has been identified in 1/251302 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |