Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000636652 | SCV000758091 | likely pathogenic | Hyper-IgM syndrome type 1 | 2021-08-12 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon(s) 2-3 of the CD40LG gene. While this deletion is not anticipated to lead to nonsense mediated decay, it is expected to disrupt the C-terminus of the protein. A similar copy number variant has been observed in individual(s) with hyper IgM syndrome (PMID: 14641931). This variant disrupts a region of the CD40LG protein in which other variant(s) (p.Gln232*) have been determined to be pathogenic (PMID: 8550833, 11158612, 18805740). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |