Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Medical Genomics, |
RCV004547426 | SCV005040768 | uncertain significance | Beta-thalassemia HBB/LCRB | 2024-05-03 | criteria provided, single submitter | clinical testing | This is a rare variant that has been observed at low allelic frequency in the South Asian population only (variant allelic frequency 0.0035%, gnomAD v4). This variant has not been described in literature, however two different missense variants at the same codon (p.Ala129Val and p.Ala129Pro, also known as Hb Sitia and Hb Mont Saint Aignan respectively) have been described as mildly unstable haemoglobin variant leading to mild chronic microcytic anaemia (PMID: 11300349, 11300350). Alanine 129 interacts with several amino acids at the alpha/beta haemoglobin subunit interface. In silico analysis by REVEL also predicted the p.(Ala129Thr) variant pathogenic (REVEL 0.70). |