Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostics Lab, |
RCV000497480 | SCV000590839 | likely pathogenic | Feingold syndrome type 1 | 2016-01-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003669152 | SCV004394881 | uncertain significance | not provided | 2022-12-23 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Arg394 amino acid residue in MYCN. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15821734, 33442900). 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 MYCN protein function. ClinVar contains an entry for this variant (Variation ID: 433153). This missense change has been observed in individual(s) with Feingold syndrome (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 394 of the MYCN protein (p.Arg394Leu). |