Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002375646 | SCV002625325 | pathogenic | Diamond-Blackfan anemia | 2015-07-09 | criteria provided, single submitter | clinical testing | The p.M1? pathogenic mutation (also known as c.3G>A), located in coding exon 1 of the RPL5 gene, results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon. In addition, this change occurs in the last base pair of coding exon 1, which makes it likely to have some effect on normal mRNA splicing. This mutation has been described in a Japanese individual with a clinical diagnosis of Diamond-Blackfan anemia (DBA), who had thumb polydactyly in addition to red blood cell aplasia (Konno Y et al. Haematologica 2010 Aug; 95(8):1293-9). Multiple other nucleotide substitutions that alter the initiation codon have also been reported in individuals with DBA (Konno Y et al. Haematologica 2010 Aug; 95(8):1293-9; Boria I et al. Hum. Mutat. 2010 Dec; 31(12):1269-79; Quarello P et al. Haematologica 2010 Feb; 95(2):206-13). In addition to the clinical data presented in the literature, since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation or N-terminal truncation, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). |