Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000157883 | SCV000207814 | likely pathogenic | not provided | 2022-06-02 | criteria provided, single submitter | clinical testing | Reported in one carrier female from a family with classic Fabry disease; however, details on affected male relatives were not provided (Shabbeer et al., 2002; Shabbeer et al., 2005); Also reported in an adult female with long-term hematuria with good renal function and cornea verticillata, but this variant was also identified in the individual's mother and sister who were reported to be asymptomatic and no male relatives were evaluated (Maixnerov et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate that this variant resulted in significant reductions of alpha-galactosidase enzyme activities in HEK293 cells (Benjamin et al., 2017); This variant is associated with the following publications: (PMID: 25382311, 15712228, 23305247, 27657681, 12175777, 28615118) |
| Genome- |
RCV001807105 | SCV002054793 | likely pathogenic | Fabry disease | 2021-07-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001807105 | SCV002309122 | pathogenic | Fabry disease | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 362 of the GLA protein (p.Pro362Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Fabry disease (PMID: 12175777, 23305247; Invitae). ClinVar contains an entry for this variant (Variation ID: 180832). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on GLA protein function. Experimental studies have shown that this missense change affects GLA function (PMID: 27657681). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV000157883 | SCV004238216 | likely pathogenic | not provided | 2023-05-18 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000157883 | SCV000707788 | uncertain significance | not provided | 2017-04-13 | flagged submission | clinical testing |