Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001237589 | SCV001410355 | pathogenic | Hyper-IgM syndrome type 1 | 2020-01-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly257 amino acid residue in CD40LG. Other variant(s) that disrupt this residue have been observed in individuals with CD40LG-related conditions (PMID: 20981468, 8889581), which suggests that this may be a clinically significant amino acid residue. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual affected with hyper-IgM syndrome (PMID: 10366125). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 257 of the CD40LG protein (p.Gly257Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |