ClinVar Miner

Submissions for variant NM_000061.3(BTK):c.176AGA[1] (p.Lys60del)

dbSNP: rs1603019594
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780070 SCV000917093 pathogenic X-linked agammaglobulinemia 2018-06-01 criteria provided, single submitter clinical testing Variant summary: BTK c.179_181delAGA (p.Lys60del) results in an in-frame deletion that is predicted to remove a Lysine from the encoded protein. The variant was absent in 178627 control chromosomes (gnomAD). The variant, c.179_181delAGA, has been reported in the literature in multiple individuals affected with X-linked Agammaglobulinemia including segregating within one large family (Pienaar_2000, Danielian_2003). The affected individuals also showed no BTK protein expression (Pienaar_2003). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000810868 SCV000951105 pathogenic X-linked agammaglobulinemia with growth hormone deficiency 2023-10-06 criteria provided, single submitter clinical testing This variant, c.179_181del, results in the deletion of 1 amino acid(s) of the BTK protein (p.Lys60del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with X-linked agammaglobulinemia (XLA) (PMID: 11036800, 12655572, 30072168). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 632728). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004723169 SCV005340111 pathogenic BTK-related disorder 2024-08-28 no assertion criteria provided clinical testing The BTK c.179_181delAGA variant is predicted to result in an in-frame deletion (p.Lys60del). This variant has been reported in individuals with X-linked agammaglobulinemia (P14, Esenboga et al. 2018. PubMed ID: 29424453; Pienaar et al. 2000. PubMed ID: 11036800; Doğruel et al. 2018. PubMed ID: 30072168; Patient 4, reported as c.310_312delAAG (p.K60del), Danielian et al. 2003. PubMed ID: 12655572). A functional study using samples from patients with this variant showed that there was no protein protein (Pienaar et al. 2000. PubMed ID: 11036800). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic.

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