Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413906 | SCV000491819 | likely pathogenic | not provided | 2016-11-23 | criteria provided, single submitter | clinical testing | The G465E variant in the CPT1A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. However, missense variants at this same codon (G465W and G465R) have been reported in individuals with CPT1 deficiency (Bennett et al., 2004; Choi et al., 2016). The G465E variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G465E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved; however in silico analysis predicts this variant is probably damaging to the protein structure/function. The G465E variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |