Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792783 | SCV000932103 | 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) 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 X-linked hyper IgM syndrome (PMID: 14641931). It has also been observed to segregate with disease in related individuals. This variant disrupts the p.Ala123, p.Thr254 amino acid residue in CD40LG. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8094231, 8889581, 10484640, 15623492, 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. |