Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001382557 | SCV001581397 | pathogenic | Hyper-IgM syndrome type 1 | 2020-01-27 | criteria provided, single submitter | clinical testing | This variant disrupts the C-terminus of the CD40LG protein. Other variant(s) that disrupt this region (p.Gln221*, p.Gln232*) have been determined to be pathogenic (PMID: 7906987, 8550833, 18805740). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with hyper-IgM syndrome (PMID: 17553565). This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the CD40LG gene (p.Asn157Metfs*5). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 105 amino acids of the CD40LG protein. |