Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001060218 | SCV001224895 | likely pathogenic | Hyper-IgM syndrome type 1 | 2022-08-31 | criteria provided, single submitter | clinical testing | 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. This variant disrupts the p.Tyr172 amino acid residue in CD40LG. Other variant(s) that disrupt this residue have been observed in individuals with CD40LG-related conditions (PMID: 22928961), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CD40LG protein function. ClinVar contains an entry for this variant (Variation ID: 855047). This missense change has been observed in individuals with hyper-IgM syndrome (HIGM) (PMID: 33060515; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 172 of the CD40LG protein (p.Tyr172His). |