ClinVar Miner

Submissions for variant NM_000061.3(BTK):c.1697C>T (p.Pro566Leu)

gnomAD frequency: 0.00001  dbSNP: rs1057521814
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000438550 SCV000524646 likely pathogenic not provided 2024-01-12 criteria provided, single submitter clinical testing Published functional studies demonstrate this variant abolishes BTK kinase activity (PMID: 33419778); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33419778, 34029777)
Labcorp Genetics (formerly Invitae), Labcorp RCV000798428 SCV000938045 uncertain significance X-linked agammaglobulinemia with growth hormone deficiency 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 566 of the BTK protein (p.Pro566Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. 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.Pro566 amino acid residue in BTK. Other variant(s) that disrupt this residue have been observed in individuals with BTK-related conditions (PMID: 23335184, 11438999), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BTK-related conditions. ClinVar contains an entry for this variant (Variation ID: 384005). This variant is not present in population databases (ExAC no frequency).
Mayo Clinic Laboratories, Mayo Clinic RCV000438550 SCV005413426 likely pathogenic not provided 2024-02-29 criteria provided, single submitter clinical testing PP2, PP3, PP4, PM1, PM2, PM5

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