Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000490123 | SCV000577168 | pathogenic | not provided | 2017-04-07 | criteria provided, single submitter | clinical testing | The Q220X nonsense variant in the CYBB gene has been reported previously in association with X-linked Hyper-IgM syndrome (Jayoussi-Assalia et al., 2000; Lee et al., 2005; Vargas-Hernández et al., 2013). While this variant is not predicted to result in nonsense-mediated decay, it is predicted to cause loss of normal protein function through protein truncation, as the final 42 amino acids are lost. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). In summary, we consider this variant to be pathogenic. |
Invitae | RCV001865515 | SCV002178368 | pathogenic | Hyper-IgM syndrome type 1 | 2022-10-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 426663). This premature translational stop signal has been observed in individual(s) with hyper IgM syndrome (PMID: 11038461, 15358621, 22963373). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln220*) in the CD40LG gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the CD40LG protein. |