ClinVar Miner

Submissions for variant NM_000061.3(BTK):c.1908+1G>T

dbSNP: rs2147423955
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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 RCV002013402 SCV002289122 likely pathogenic X-linked agammaglobulinemia with growth hormone deficiency 2021-05-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 18 of the BTK gene. RNA analysis indicates that this variant induces altered splicing and likely results in the loss of 11 amino acid residue(s), but is expected to preserve the integrity of the reading-frame. This variant is not present in population databases (ExAC no frequency). 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 variant disrupts the p.Trp634 amino acid residue in BTK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 12655572, 27512878, 25777788). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant is associated with the activation of a cryptic splice site in exon 18 (PMID: 11027452). Disruption of this splice site has ‚Äãbeen observed in individual(s) with X-linked agammaglobulinemia ‚Äã‚Äã(PMID: 11027452, 9260159, 1240516). This variant is also known as c.2040+1G>T in the literature.

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