Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001267354 | SCV001445535 | likely pathogenic | Inborn genetic diseases | 2020-01-29 | criteria provided, single submitter | clinical testing | The alteration results in a premature stop codon: The c.1037dupC (p.Q347Tfs*22) alteration, located in exon 3 (coding exon 2) of the MYCN gene, consists of a duplication of C at position 1037, causing a translational frameshift with a predicted alternate stop codon after 22 amino acids. This alteration occurs in the last exon of the MYCN gene, so while it is truncating, the mRNA is predicted to escape nonsense mediated decay (NMD) and a truncated mutant protein could still be expressed. Premature termination codons located either in the last exon or within 50-55 nucleotides upstream of the 3’-most exon-exon junction usually fail to elicit nonsense mediated decay (NMD) (Maquat, 2004). The exact functional impact of the truncation is unknown at this time; however, additional frameshift alterations downstream of this alteration have been reported in the literature as disease-causing (van Bokhoven, 2005). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the MYCN c.1037dupC alteration was not observed, with coverage at this position. Based on the available evidence, this alteration is classified as likely pathogenic. |