Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001936287 | SCV002201235 | uncertain significance | not provided | 2021-08-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asp37Glufs*20) in the APOA5 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 330 amino acid(s) of the APOA5 protein. This variant is not present in population databases (ExAC no frequency). 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. This variant has not been reported in the literature in individuals affected with APOA5-related conditions. |
| Ambry Genetics | RCV004041853 | SCV003620320 | pathogenic | Cardiovascular phenotype | 2022-06-21 | criteria provided, single submitter | clinical testing | The c.111delC (p.D37Efs*20) alteration, located in exon 3 (coding exon 2) of the APOA5 gene, consists of a deletion of one nucleotide at position 111, causing a translational frameshift with a predicted alternate stop codon after 20 amino acids. This alteration occurs at the 3’ terminus of the APOA5 gene and is not expected to trigger nonsense-mediated mRNA decay. However, premature stop codons are typically deleterious in nature, and this variant results in the loss of approximately 89% of the protein, including a C-terminal domain that has been implicated in lipid binding (Sun, 2006). Based on data from gnomAD, the c.111delC allele has an overall frequency of <0.01% (2/242778) total alleles studied. The highest observed frequency was 0.01% (1/15516) of African alleles. Based on the available evidence, this alteration is classified as pathogenic. |