ClinVar Miner

Submissions for variant NM_000061.3(BTK):c.371G>A (p.Trp124Ter)

dbSNP: rs1555980049
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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 RCV000586376 SCV000695288 likely pathogenic X-linked agammaglobulinemia 2017-01-24 criteria provided, single submitter clinical testing Variant summary: The BTK c.371G>A (p.Trp124X) variant results in a premature termination codon, predicted to cause a truncated or absent BTK protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.982C>T, p.Gln328X; c.1455C>A, p.Tyr485X; c.1558C>T, p.Arg520X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 86517 control chromosomes but has been reported in at least 2 affected individuals in the literature (Wang_2009, Hashimoto_1996). Taken together, this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003512058 SCV004300178 pathogenic X-linked agammaglobulinemia with growth hormone deficiency 2022-11-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 492811). This variant is also known as 503G>A. This premature translational stop signal has been observed in individual(s) with X-linked agammaglobulinemia (PMID: 8695804). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp124*) in the BTK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BTK are known to be pathogenic (PMID: 15661032, 16862044, 19419768).
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital RCV000584393 SCV000692186 pathogenic Autosomal recessive agammaglobulinemia 1 2009-07-21 no assertion criteria provided clinical testing

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