Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000494020 | SCV000583155 | likely pathogenic | not provided | 2015-08-06 | criteria provided, single submitter | clinical testing | The R124P variant has not been published as a pathogenic variant or as a benign polymorphism to our knowledge. The R124P 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 conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in a nearby residue (R124Q) has been reported in the Human Gene Mutation Database in association with carnitine palmitoyltransferase II (CPT2) deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded |
| Eurofins Ntd Llc |
RCV000494020 | SCV000862738 | uncertain significance | not provided | 2018-07-31 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002527108 | SCV003032728 | likely pathogenic | Carnitine palmitoyltransferase II deficiency | 2022-07-01 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CPT2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 124 of the CPT2 protein (p.Arg124Pro). ClinVar contains an entry for this variant (Variation ID: 430363). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg124 amino acid residue in CPT2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12673791). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CPT2 protein function. |