Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000649344 | SCV000771171 | uncertain significance | Mosaic variegated aneuploidy syndrome 2 | 2024-03-06 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 125 of the CEP57 protein (p.His125Tyr). This variant is present in population databases (rs751973626, gnomAD 0.03%). 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: 539587). 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 | RCV004972810 | SCV005561106 | uncertain significance | Inborn genetic diseases | 2024-11-24 | criteria provided, single submitter | clinical testing | The p.H125Y variant (also known as c.373C>T), located in coding exon 3 of the CEP57 gene, results from a C to T substitution at nucleotide position 373. The histidine at codon 125 is replaced by tyrosine, an amino acid with similar 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. |
Fulgent Genetics, |
RCV000649344 | SCV005631471 | uncertain significance | Mosaic variegated aneuploidy syndrome 2 | 2024-04-10 | criteria provided, single submitter | clinical testing |