Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000649343 | SCV000771170 | uncertain significance | Mosaic variegated aneuploidy syndrome 2 | 2024-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 431 of the CEP57 protein (p.Glu431Ala). This variant is present in population databases (rs367799359, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CEP57-related conditions. ClinVar contains an entry for this variant (Variation ID: 539586). 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 not expected to disrupt CEP57 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. |
| Ambry Genetics | RCV004972809 | SCV005561114 | uncertain significance | Inborn genetic diseases | 2024-11-25 | criteria provided, single submitter | clinical testing | The p.E431A variant (also known as c.1292A>C), located in coding exon 11 of the CEP57 gene, results from an A to C substitution at nucleotide position 1292. The glutamic acid at codon 431 is replaced by alanine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |