Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004337710 | SCV004067823 | uncertain significance | Cardiovascular phenotype | 2023-07-25 | criteria provided, single submitter | clinical testing | The c.1606C>G (p.P536A) alteration is located in exon 12 (coding exon 12) of the APOB gene. This alteration results from a C to G substitution at nucleotide position 1606, causing the proline (P) at amino acid position 536 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999927 | SCV005624799 | uncertain significance | not provided | 2024-07-26 | criteria provided, single submitter | clinical testing | The APOB c.1606C>G (p.Pro536Ala) variant has not been reported in individuals with APOB-related conditions in the published literature. The frequency of this variant in the general population, 0.000004 (1/251256 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Labcorp Genetics |
RCV005228019 | SCV005865183 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2024-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 536 of the APOB protein (p.Pro536Ala). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of familial hypercholesterolemia (internal data). ClinVar contains an entry for this variant (Variation ID: 2593731). 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) indicates that this missense variant is not expected to disrupt APOB protein function with a negative predictive value of 95%. 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. |