Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| LDLR- |
RCV000237429 | SCV000295330 | likely pathogenic | Hypercholesterolemia, familial, 1 | 2016-03-25 | criteria provided, single submitter | literature only | |
| Invitae | RCV001238043 | SCV001410837 | uncertain significance | Familial hypercholesterolemia | 2019-09-24 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Tyr419 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 30270081), which suggests that this may be a clinically significant amino acid residue. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 and their clinical significance is uncertain. This variant has been observed in an individual affected with familial hypercholesterolemia (PMID: 19717150). This variant is also known as Y398H in the literature. ClinVar contains an entry for this variant (Variation ID: 251756). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 419 of the LDLR protein (p.Tyr419His). The tyrosine residue is highly conserved and there is a moderate physicochemical difference between tyrosine and histidine. |
| Laboratorium voor Moleculaire Diagnostiek Experimentele Vasculaire Geneeskunde, |
RCV000237429 | SCV000606376 | pathogenic | Hypercholesterolemia, familial, 1 | no assertion criteria provided | research |