Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000011480 | SCV000695746 | pathogenic | Fabry disease | 2021-03-23 | criteria provided, single submitter | clinical testing | Variant summary: GLA c.791A>T (p.Asp264Val) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 183472 control chromosomes (gnomAD). c.791A>T has been reported in the literature in at least three unrelated individuals affected with Classic Fabry Disease (example: Eng_1993, Wu_2011, Brown_1997). These data indicate that the variant is likely to be associated with disease. In vitro functional assays show that this variant has no enzymatic activity (example: Wu_2011, Lukas_2013). One other ClinVar submitter (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Eurofins Ntd Llc |
RCV000724649 | SCV000700796 | pathogenic | not provided | 2018-09-12 | criteria provided, single submitter | clinical testing | |
| Genome- |
RCV000011480 | SCV002054406 | pathogenic | Fabry disease | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000011480 | SCV002292790 | likely pathogenic | Fabry disease | 2021-03-29 | criteria provided, single submitter | clinical testing | 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.Asp264 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 15712228), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this variant affects GLA protein function (PMID: 21598360). This variant has been observed in individual(s) with Fabry disease (PMID: 7504405, 19387866, 9116979). ClinVar contains an entry for this variant (Variation ID: 10734). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with valine at codon 264 of the GLA protein (p.Asp264Val). The aspartic acid residue is highly conserved and there is a large physicochemical difference between aspartic acid and valine. |
| OMIM | RCV000011480 | SCV000031712 | pathogenic | Fabry disease | 1993-12-01 | no assertion criteria provided | literature only |