Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000237270 | SCV000294538 | likely benign | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Cardiovascular Research Group, |
RCV000237270 | SCV000322879 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-01 | criteria provided, single submitter | research | 0/100 normolipidemic individuals |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000237270 | SCV000503113 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subject mutated among 2600 FH index cases screened = 1 , family member = 1 with co-segregation / mild phenotype / Software predictions: Damaging |
U4M - |
RCV000237270 | SCV000583641 | likely pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Color | RCV001182218 | SCV001347577 | likely benign | Familial hypercholesterolemia | 2017-05-15 | criteria provided, single submitter | clinical testing | |
Broad Institute Rare Disease Group, |
RCV001182218 | SCV001423041 | uncertain significance | Familial hypercholesterolemia | 2020-01-22 | no assertion criteria provided | curation | The p.Gly76Trp variant in LDLR has been reported in at least 1 Portuguese individual with familial hypercholesterolemia (PMID: 17765246), and was absent from large population studies. This variant has also been reported in ClinVar as having conflicting interpretations of pathogenicity (Variation ID: rs574337291). In vitro functional studies provide some evidence that the p.Gly76Trp variant may not impact protein function (PMID: 25741862). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Gly76Trp variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3, BS3_supporting (Richards 2015). |