Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
LDLR- |
RCV000211590 | SCV000295774 | uncertain significance | Familial hypercholesterolemia 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
Centre de Génétique Moléculaire et Chromosomique, |
RCV000211590 | SCV000503437 | likely pathogenic | Familial hypercholesterolemia 1 | 2016-12-16 | criteria provided, single submitter | clinical testing | subjects mutated among 2600 FH index cases screened = 2 / Other mutation at same codon/Software predictions: Conflicting |
U4M - |
RCV000211590 | SCV000583911 | likely pathogenic | Familial hypercholesterolemia 1 | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000775082 | SCV000627024 | likely pathogenic | Familial hypercholesterolemia | 2019-02-06 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine with threonine at codon 652 of the LDLR protein (p.Met652Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in several unrelated individuals affected with hypercholesterolemia (PMID: 20236128, 20809525, Invitae). ClinVar contains an entry for this variant (Variation ID: 226382). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
Color | RCV000775082 | SCV000909186 | uncertain significance | Familial hypercholesterolemia | 2020-03-26 | criteria provided, single submitter | clinical testing | |
Cardiovascular Genetics Laboratory, |
RCV000211590 | SCV000268651 | pathogenic | Familial hypercholesterolemia 1 | 2008-06-25 | no assertion criteria provided | clinical testing |