Submissions for variant NM_005378.6(MYCN):c.134del (p.Pro45fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV003239074	SCV003936399	pathogenic	not provided	2023-06-29	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18470948)
Molecular Genetics Department, Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology	RCV003985880	SCV004801847	likely pathogenic	Feingold syndrome type 1		criteria provided, single submitter	clinical testing	A previously undescribed nucleotide variant creates a frameshift p.Pro45ArgfsTer86 in the MYCN gene. The variant was observed in heterozygous state in an individual affected with duodenal obstruction. Loss-of-function variants are reported in patients with Feingold syndrome 1, 164280. The call is present in gnomAD population database at low frequency (2/248124 chromosomes, no homozygotes), however those calls do not pass quality control and cannot be assumed to be true variants. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as likely pathogenic.