Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000825531 | SCV000966846 | likely pathogenic | Autosomal recessive distal spinal muscular atrophy 1 | 2018-10-26 | criteria provided, single submitter | clinical testing | The p.Ser244ProfsX41 variant in IGHMBP2 has not been previously reported in indi viduals with Spinal muscular atrophy with respiratory distress type 1 (SMARD1) a nd was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at positi on 244 and leads to a premature termination codon 41 amino acids downstream. Thi s alteration is then predicted to lead to a truncated or absent protein. Biallel ic loss of function of the IGHMBP2 gene is an established disease mechanism in S MARD1. In summary, although additional studies are required to fully establish i ts clinical significance, the p.Ser244ProfsX41 variant is likely pathogenic. ACM G/AMP Criteria applied: PVS1, PM2. |