Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001305459 | SCV001494794 | uncertain significance | Familial hypercholesterolemia | 2020-07-21 | criteria provided, single submitter | clinical testing | The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This sequence change replaces valine with alanine at codon 653 of the LDLR protein (p.Val653Ala). The valine residue is highly conserved and there is a small physicochemical difference between valine and alanine. This variant has been observed in individual(s) with hypercholesterolemia (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). This variant disrupts the p.Val653 amino acid residue in LDLR. Other variant(s) that disrupt this residue have been observed in individuals with LDLR-related conditions (PMID: 14974088, 30592178, 20809525), 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. |