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 | 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. This variant is not present in population databases (ExAC no frequency). 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. |
| 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. |