Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV002810026 | SCV003761253 | pathogenic | Iron-refractory iron deficiency anemia | 2023-01-25 | criteria provided, single submitter | curation | The homozygous p.Ser352Ter variant in TMPRSS6 was identified by our study in one individual with iron-refractory iron deficiency anemia (IRIDA) syndrome. The p.Ser352Ter variant has not been previously reported in individuals with iron-refractory iron deficiency anemia (IRIDA) syndrome. This variant was absent from large population studies. The affected individual identified by our study was a homozygote, which increases the likelihood that the p.Ser352Ter variant is pathogenic. This nonsense variant leads to a premature termination codon at position 352, which is predicted to lead to a truncated or absent protein. Loss of function is an established disease mechanism in autosomal recessive iron-refractory iron deficiency anemia (IRIDA) syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive iron-refractory iron deficiency anemia (IRIDA) syndrome. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3_Supporting (Richards 2015). |