Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001217870 | SCV001389728 | uncertain significance | Fabry disease | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with proline at codon 115 of the GLA protein (p.His115Pro). The histidine residue is weakly conserved and there is a moderate physicochemical difference between histidine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GLA-related conditions. 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 tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002451489 | SCV002617040 | uncertain significance | Cardiovascular phenotype | 2021-05-18 | criteria provided, single submitter | clinical testing | The p.H115P variant (also known as c.344A>C), located in coding exon 2 of the GLA gene, results from an A to C substitution at nucleotide position 344. The histidine at codon 115 is replaced by proline, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |