Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001226443 | SCV001398756 | likely pathogenic | Fabry disease | 2019-08-13 | criteria provided, single submitter | clinical testing | 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 an individual affected with Anderson-Fabry disease (PMID: 27585509). This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with serine at codon 273 of the GLA protein (p.Phe273Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |