Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000627817 | SCV000748694 | pathogenic | Fabry disease | 2021-10-15 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Trp47 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11668641, 27211852). 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. This missense change has been observed in individual(s) with Fabry disease (Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with cysteine at codon 47 of the GLA protein (p.Trp47Cys). The tryptophan residue is highly conserved and there is a large physicochemical difference between tryptophan and cysteine. |
Revvity Omics, |
RCV003488739 | SCV004235154 | uncertain significance | not provided | 2023-05-26 | criteria provided, single submitter | clinical testing |