Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
3billion | RCV003153189 | SCV003842054 | pathogenic | Fabry disease | 2023-02-23 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. Missense changes are a common disease-causing mechanism. Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID: 19287194, 20505683, 27657681). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.93; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with GLA related disorder (PMID: 11076046 / 3billion dataset). Different missense changes at the same codon (p.Asp266Ala, p.Asp266Glu, p.Asp266Gly, p.Asp266His, p.Asp266Tyr, p.Asp266Val) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000010735 / PMID: 10916280, 12428061, 18849176, 23568732, 33204599, 7504405). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. |