Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV001525293 | SCV001735351 | uncertain significance | Fabry disease | 2021-01-26 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with tryptophan at codon 189 of the GLA protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/203496 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002343708 | SCV002653224 | uncertain significance | Cardiovascular phenotype | 2021-07-02 | criteria provided, single submitter | clinical testing | The p.L189W variant (also known as c.566T>G), located in coding exon 4 of the GLA gene, results from a T to G substitution at nucleotide position 566. The leucine at codon 189 is replaced by tryptophan, an amino acid with similar properties. Based on data from gnomAD, the G allele has an overall frequency of <0.01% (2/203496) total alleles studied, with 1 hemizygote(s) observed. The highest observed frequency was <0.01% (2/91885) of European (non-Finnish) alleles. This amino acid position is not well 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. |