Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001041450 | SCV001205070 | likely pathogenic | Fabry disease | 2020-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with proline at codon 297 of the GLA protein (p.Ser297Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. 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. This variant disrupts the p.Ser297 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 31620600, 20505683, 19287194, 12428061, 19287194, 7504405). 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 individual(s) with Fabry disease (PMID: 26238931). ClinVar contains an entry for this variant (Variation ID: 839647). This variant is not present in population databases (ExAC no frequency). |