Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781427 | SCV000919445 | likely pathogenic | Fabry disease | 2019-06-19 | criteria provided, single submitter | clinical testing | Variant summary: GLA c.119C>T (p.Pro40Leu) 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 178720 control chromosomes. c.119C>T has been reported in the literature in individuals affected with Fabry Disease (Lenders_2016, Morrone_2003, Ashton-Prolla_2000). In one report, the patient had <10% WT alpha-galactosidase activity in leucocytes, further supporting the pathogenic outcome of this variant (Morrone_2003). Other variants at the same codon position have been reported as pathogenic or likely pathogenic in ClinVar and HGMD, suggesting this codon is a potential hotspot for mutation (p.Pro40Arg, p.Pro40Ser). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Labcorp Genetics |
RCV000781427 | SCV001587277 | pathogenic | Fabry disease | 2020-03-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro40 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 2152885, 26415523, 20367968, 19320660), which suggests that this may be a clinically significant amino acid residue. This variant has been reported to affect GLA protein function (PMID: 27657681). This variant has been observed in individual(s) with Fabry disease (PMID: 12920095, 10916280, 27356758, Invitae). ClinVar contains an entry for this variant (Variation ID: 633248). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with leucine at codon 40 of the GLA protein (p.Pro40Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |
| Genome- |
RCV000781427 | SCV002054460 | likely pathogenic | Fabry disease | 2021-07-15 | criteria provided, single submitter | clinical testing |