ClinVar Miner

Submissions for variant NM_000061.3(BTK):c.1559G>T (p.Arg520Leu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003625551 SCV004430024 uncertain significance X-linked agammaglobulinemia with growth hormone deficiency 2023-02-01 criteria provided, single submitter clinical testing 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 affected with BTK-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 520 of the BTK protein (p.Arg520Leu). This variant disrupts the p.Arg520 amino acid residue in BTK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7849721, 7880320, 11472359, 12217331, 12655572, 15661032, 18677443, 27980540). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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