ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.496_497delinsGG (p.Leu166Gly)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820056 SCV000960749 pathogenic Fabry disease 2018-12-04 criteria provided, single submitter clinical testing 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Fabry disease (PMID: 16595074, http://www.dbfgp.org/dbFgp/fabry/, Invitae). 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. 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. For these reasons, this variant has been classified as Pathogenic.

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