Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000818235 | SCV000958836 | pathogenic | Hyper-IgM syndrome type 1 | 2023-03-27 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Thr254 amino acid residue in CD40LG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8889581, 10484640, 25541662). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 660932). This premature translational stop signal has been observed in individuals with clinical features of hyper IgM syndrome (PMID: 7906987; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln221*) in the CD40LG gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the CD40LG protein. |