Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780074 | SCV000917097 | pathogenic | X-linked agammaglobulinemia | 2023-01-25 | criteria provided, single submitter | clinical testing | Variant summary: BTK c.1138C>T (p.Gln380X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant was absent in 183516 control chromosomes (gnomAD). c.1138C>T has been reported in the literature in individuals affected with X-Linked Agammaglobulinemia (example: Conley_2005 and Khan_2021). These data indicate that the variant is associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV001055303 | SCV001219690 | pathogenic | X-linked agammaglobulinemia with growth hormone deficiency | 2024-03-14 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln380*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked agammaglobulinemia (PMID: 15661032). ClinVar contains an entry for this variant (Variation ID: 632732). For these reasons, this variant has been classified as Pathogenic. |