Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001838114 | SCV000832402 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2018-03-23 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with APOB-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. A different missense substitution at this codon (p.Tyr3560Cys) has been reported in individuals affected with familial hypercholesterolemia (PMID: 18325181, 20828696). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 3560 of the APOB protein (p.Tyr3560His). The tyrosine residue is moderately conserved and there is a moderate physicochemical difference between tyrosine and histidine. |