Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
MVZ Dr. |
RCV001290761 | SCV001478893 | pathogenic | not provided | 2020-01-17 | criteria provided, single submitter | clinical testing | This variant is absent from controls in Exome Sequencing Project, 1000 Genomes Project and Exome Aggregation Consortium. The deletion of 5 basepairs in exon 9 creates a frame shift starting at codon Ala234. The new reading frame ends in a stop codon at position 37 (p.Ala234Leufs*37). Therefore the mutation is a null variant in a gene where loss of function is a known mechanism of diesease. The mutation probably effects the cytoplasmatic domain, which mediates the interaction between Band 3 and the membrane skeleton via ANK1, EPB41 and EPB42. In case of a premature stop codon at the predicted position the transmembrane domain would be missing. The variants Princeton (p.H275Pfs*96) (Jarolim et al. 1996, PMID: 8943874) and Noirterre (p.Q330X) (Jenkins et al. 1996, PMID: 8567957), downstream the affected location, were related to mild hereditery spherocytosis and the mutated mRNA was either not detectable or nearly absent. |