Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001214704 | SCV001386401 | uncertain significance | not provided | 2024-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 211 of the ABCG8 protein (p.Arg211Gln). This variant is present in population databases (rs777288244, gnomAD 0.009%). This missense change has been observed in individual(s) with familial hypercholesterolemia (PMID: 32088153). ClinVar contains an entry for this variant (Variation ID: 944331). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ABCG8 protein function. 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. |
Ambry Genetics | RCV004033938 | SCV004910796 | likely benign | Cardiovascular phenotype | 2024-03-14 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Prevention |
RCV004743329 | SCV005351049 | uncertain significance | ABCG8-related disorder | 2024-05-13 | no assertion criteria provided | clinical testing | The ABCG8 c.632G>A variant is predicted to result in the amino acid substitution p.Arg211Gln. This variant has been reported in at least one individual with hypercholesterolemia (Reeskamp et al. 2020. PubMed ID: 32088153). This variant is reported in 0.011% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |