Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV005465646 | SCV006134591 | uncertain significance | Inborn genetic diseases | 2025-04-10 | criteria provided, single submitter | clinical testing | The c.1370G>A (p.R457H) alteration is located in exon 13 (coding exon 12) of the PEX5 gene. This alteration results from a G to A substitution at nucleotide position 1370, causing the arginine (R) at amino acid position 457 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV002011907 | SCV002218198 | uncertain significance | Peroxisome biogenesis disorder 2B | 2024-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 457 of the PEX5 protein (p.Arg457His). This variant is present in population databases (rs758827048, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with PEX5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1447480). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PEX5 protein function with a negative predictive value of 80%. 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. |