Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003064755 | SCV003445368 | likely pathogenic | X-linked agammaglobulinemia with growth hormone deficiency | 2022-06-19 | 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.Ala582 amino acid residue in BTK. Other variant(s) that disrupt this residue have been observed in individuals with BTK-related conditions (PMID: 19904586), 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 BTK protein function. This missense change has been observed in individuals with X-linked agammaglobulinemia (PMID: 7711734, 11742281). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 582 of the BTK protein (p.Ala582Val). |