ClinVar Miner

Submissions for variant NM_000061.3(BTK):c.1558C>G (p.Arg520Gly)

dbSNP: rs128621201
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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 RCV000637052 SCV000758500 likely pathogenic X-linked agammaglobulinemia with growth hormone deficiency 2018-03-13 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with X-linked agammaglobulinemia (PMID: 12655572). This variant is also known as c.1690C>G in the literature. 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. A different missense substitution at this codon (p.Arg520Gln) has been determined to be pathogenic (PMID: 12655572, 7849721, 11472359, 7880320, 12217331, 15661032, 18677443, 27980540). This suggests that the arginine residue is critical for BTK protein function and that other missense substitutions at this position may also be pathogenic. 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 sequence change replaces arginine with glycine at codon 520 of the BTK protein (p.Arg520Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.

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