Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780073 | SCV000917096 | pathogenic | X-linked agammaglobulinemia | 2017-12-13 | criteria provided, single submitter | clinical testing | Variant summary: The BTK c.655delG (p.Val219LeufsX10) 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., p.Asp239fsX38 and p.Gln260X). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 178855 control chromosomes, but has been identified in several male patients with X-linked agammaglobulinemia and severely reduced BTK expression in B-cell lineages. Taken together, this variant is classified as pathogenic. |
| Invitae | RCV003512079 | SCV004300174 | pathogenic | X-linked agammaglobulinemia with growth hormone deficiency | 2023-12-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val219Leufs*10) 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: 10887125, 33042921, 34975878). This variant is also known as deletion of G787, c.757del (p.Val253Leufs*10). ClinVar contains an entry for this variant (Variation ID: 632731). For these reasons, this variant has been classified as Pathogenic. |