Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001234707 | SCV001407365 | uncertain significance | Familial hypercholesterolemia | 2019-08-17 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with asparagine at codon 393 of the LDLR protein (p.Lys393Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. 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 with clinical features of familial hypercholesterolemia (Invitae). This variant is not present in population databases (ExAC no frequency). |