Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002367211 | SCV002666747 | likely pathogenic | Maturity onset diabetes mellitus in young | 2017-08-23 | criteria provided, single submitter | clinical testing | The c.671_672dupAG variant, located in coding exon 2 of the PDX1 gene, results from a duplication of AG at nucleotide position 671, causing a translational frameshift with a predicted alternate stop codon (p.Q225Sfs*6). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of PDX1, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 64 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time; however, this frameshift impacts a signalling motif indicated to be needed for regulation of the degradation and translocation of PDX1 (Zhou G et al. Curr. Mol. Med., 2013 Mar;13:377-86). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |