ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.1132dup (p.Cys378fs)

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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 RCV003510691 SCV004261895 pathogenic Fabry disease 2024-01-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys378Leufs*2) in the GLA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 52 amino acid(s) of the GLA protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GLA-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the GLA protein in which other variant(s) (p.Thr412Serfs*) have been determined to be pathogenic (PMID: 1668641, 16595074, 20505683, 22551898, 23935525, 28728877, 30386727; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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