Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001970547 | SCV002255841 | uncertain significance | X-linked agammaglobulinemia with growth hormone deficiency | 2021-06-05 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Ile355 amino acid residue in BTK. Other variant(s) that disrupt this residue have been observed in individuals with BTK-related conditions (PMID: 19419768), 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 been observed in individual(s) with X-linked recessive agammaglobulinemia (XLA) (PMID: 20721470). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 355 of the BTK protein (p.Ile355Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |