Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001034790 | SCV001198089 | uncertain significance | Familial hypercholesterolemia | 2021-09-01 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with glycine at codon 789 of the LDLR protein (p.Ala789Gly). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with LDLR-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Color Diagnostics, |
RCV001034790 | SCV004359070 | uncertain significance | Familial hypercholesterolemia | 2023-11-22 | criteria provided, single submitter | clinical testing | This missense variant (also known as p.Ala768Gly in the mature protein) replaces alanine with glycine at codon 789 of the LDLR protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with LDLR-related disorders in the literature. This variant has been identified in 1/31386 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Natera, |
RCV001034790 | SCV001461332 | uncertain significance | Familial hypercholesterolemia | 2020-09-16 | no assertion criteria provided | clinical testing |