Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001047256 | SCV001211197 | pathogenic | Fabry disease | 2019-01-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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 to segregate with Fabry disease in a family (PMID: 23305247) and has been observed in mutiple individuals affected with Fabry disease (PMID: 12175777, 11914245, 17040996, 18023222). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 317 of the GLA protein (p.Ile317Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. |