Submissions for variant NM_000169.3(GLA):c.989A>G (p.Gln330Arg)

dbSNP: rs869312161

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000209009	SCV001422924	uncertain significance	Fabry disease	2020-01-22	criteria provided, single submitter	curation	The p.Gln330Arg variant in GLA has been reported in the literature in three males, whose clinical status for Fabry disease was uncertain (PMID: 26415523, 29330335, 28340804), and was absent from large population studies (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs869312161). This variant has also been reported in ClinVar as a VUS by the Albrecht-Kossel-Institute (Variation ID: 217409). In vitro functional studies provide some evidence that the p.Gln330Arg variant may not impact protein function (PMID: 26415523). However, these types of assays may not accurately represent biological function. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of p.Gln330Arg is uncertain. ACMG/AMP Criteria applied: PM2, BP4, BS3_supporting (Richards 2015).
Albrecht-Kossel-Institute, Medical University Rostock	RCV000209009	SCV000246095	uncertain significance	Fabry disease	2014-01-01	no assertion criteria provided	research
Albrecht-Kossel-Institute, Medical University Rostock	RCV000209395	SCV000246096	drug response	Migalastat response	2014-01-01	no assertion criteria provided	research