Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001267169 | SCV001445350 | likely pathogenic | Inborn genetic diseases | 2021-11-17 | criteria provided, single submitter | clinical testing | The c.3042dupA (p.E1015Rfs*27) alteration, located in exon 24 (coding exon 20) of the ZMIZ1 gene, consists of a duplication of A at position 3042, causing a translational frameshift with a predicted alternate stop codon after 27 amino acids. This alteration occurs at the 3' terminus of the ZMIZ1 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 5% of the protein. However, premature stop codons are typically deleterious in nature and another alteration resulting in the same truncation position (p.T1038Nfs*4) has been reported in the literature as disease-causing (Carapito, 2018). In addition, the truncated region contains a functionally important protein domain (see below). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). The p.E1015Rfs*27 alteration is predicted to affect the last 53 amino acids of the protein, which involves the transactivation domain (TAD). The TAD has been shown to induce transcription of Myc transcripts and drive proliferation (Pinnell, 2015). Based on the available evidence, this alteration is classified as likely pathogenic. |
| Institute of Medical Genetics and Applied Genomics, |
RCV001268854 | SCV001448060 | likely pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing |