Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001984261 | SCV002280421 | likely pathogenic | X-linked agammaglobulinemia with growth hormone deficiency | 2020-12-24 | 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.Trp588 amino acid residue in BTK. Other variant(s) that disrupt this residue have been observed in individuals with BTK-related conditions (PMID: 14974089, 17045652, 26931785), 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 variant has not been reported in the literature in individuals with BTK-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with leucine at codon 588 of the BTK protein (p.Trp588Leu). The tryptophan residue is highly conserved and there is a small physicochemical difference between tryptophan and leucine. |