Submissions for variant NM_005378.6(MYCN):c.1180C>T (p.Arg394Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002706362	SCV003007217	uncertain significance	not provided	2022-11-23	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; Invitae). 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. 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 cysteine, which is neutral and slightly polar, at codon 394 of the MYCN protein (p.Arg394Cys).
GeneDx	RCV002706362	SCV005685951	likely pathogenic	not provided	2025-02-02	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 19921653, 15821734, 18470948, 33442900)