Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001236826 | SCV001409564 | pathogenic | Fabry disease | 2019-09-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Tyr216 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19941952, 20367968, 27560961, 28756410). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in several individuals affected with Fabry disease (PMID: 25386848, 9100224, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with aspartic acid at codon 216 of the GLA protein (p.Tyr216Asp). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and aspartic acid. |