Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000596465 | SCV000706496 | pathogenic | not provided | 2018-02-20 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001000881 | SCV001157963 | pathogenic | not specified | 2019-01-03 | criteria provided, single submitter | clinical testing | The ABCA4 c.123G>A; p.Trp41Ter variant (rs748357067), to our knowledge, is not reported in the medical literature. However, another variant in the same codon leading to the same premature termination codon, c.122G>A; p.Trp41Ter has been reported in individuals with Stargardt or ABCA4-related disease (Cideciyan 2009, Jaakson 2003). The c.123G>A variant has been reported as pathogenic in the ClinVar database (Variation ID: 500506) and in the Genome Aggregation Database in 1 out of 251406 alleles, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Considering available information, this variant is classified as pathogenic. References: Cideciyan AV et al. ABCA4 disease progression and a proposed strategy for gene therapy. Hum Mol Genet. 2009 Mar 1;18(5):931-41. Jaakson K et al. Genotyping microarray (gene chip) for the ABCR (ABCA4) gene. Hum Mutat. 2003 Nov;22(5):395-403. |
Invitae | RCV000596465 | SCV001592718 | pathogenic | not provided | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp41*) in the ABCA4 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ABCA4 are known to be pathogenic (PMID: 10958761, 24938718, 25312043, 26780318). This variant is present in population databases (rs748357067, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with ABCA4-related disease (PMID: 25444351, 30670881). ClinVar contains an entry for this variant (Variation ID: 500506). For these reasons, this variant has been classified as Pathogenic. |