Submissions for variant NM_000169.3(GLA):c.59C>A (p.Ala20Asp)

dbSNP: rs869312134

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000209573	SCV001212709	pathogenic	Fabry disease	2022-11-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Ala20 amino acid residue in GLA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7596372, 17555407, 23935525, 26415523, 27657681). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects GLA function (PMID: 26415523, 27657681). 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 217373). This missense change has been observed in individual(s) with Fabry disease (PMID: 33204599; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 20 of the GLA protein (p.Ala20Asp).
Fulgent Genetics, Fulgent Genetics	RCV000209573	SCV002796765	likely pathogenic	Fabry disease	2021-11-02	criteria provided, single submitter	clinical testing
Albrecht-Kossel-Institute, Medical University Rostock	RCV000209573	SCV000246019	pathogenic	Fabry disease	2014-01-01	no assertion criteria provided	research
Albrecht-Kossel-Institute, Medical University Rostock	RCV000208891	SCV000246020	drug response	Migalastat response	2014-01-01	no assertion criteria provided	research