Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003509069 | SCV004299626 | pathogenic | Fabry disease | 2023-05-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the GLA protein in which other variant(s) (p.Ile317Thr) have been determined to be pathogenic (PMID: 11914245, 12175777, 17040996, 18023222, 23305247). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this premature translational stop signal affects GLA function (PMID: 23935525). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant is also known as c948InsT. This premature translational stop signal has been observed in individual(s) with Fabry disease (PMID: 23935525). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile317Asnfs*16) in the GLA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 113 amino acid(s) of the GLA protein. |