Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000820056 | SCV000960749 | pathogenic | Fabry disease | 2018-11-24 | criteria provided, single submitter | clinical testing | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu166 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 17555407, 7759078), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. This variant has been observed in several individuals affected with Fabry disease (PMID: 16595074, http://www.dbfgp.org/dbFgp/fabry/, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with glycine at codon 166 of the GLA protein (p.Leu166Gly). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and glycine. |