ClinVar Miner

Submissions for variant NM_000061.3(BTK):c.1747T>G (p.Phe583Val)

dbSNP: rs1926378381
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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 RCV001057292 SCV001221777 likely pathogenic X-linked agammaglobulinemia with growth hormone deficiency 2019-01-07 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with valine at codon 583 of the BTK protein (p.Phe583Val). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with X-linked agammaglobulinemia (PMID: 19419768). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant disrupts the p.Phe583 amino acid residue in BTK. Other variant(s) that disrupt this residue have been observed in individuals with BTK-related conditions (PMID:21039741, 9445504), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. 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.

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