Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174740 | SCV001338046 | pathogenic | Fabry disease | 2020-01-09 | criteria provided, single submitter | clinical testing | Variant summary: GLA c.295C>T (p.Gln99X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 183486 control chromosomes (gnomAD). c.295C>T has been reported in the literature in individuals affected with Fabry Disease (Eng_1994, Militaru_2019). At least one publication reports this variant results in decreased enzyme activity in a patient (Topaloglu_1999). 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 pathogenic. |
| Ambry Genetics | RCV002436730 | SCV002751988 | pathogenic | Cardiovascular phenotype | 2020-03-28 | criteria provided, single submitter | clinical testing | The p.Q99* pathogenic mutation (also known as c.295C>T), located in coding exon 2 of the GLA gene, results from a C to T substitution at nucleotide position 295. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This mutation has been reported in an individual with classic Fabry disease (Eng CM et al. Hum. Mol. Genet., 1994 Oct;3:1795-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |