ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.865A>G (p.Ile289Val) (rs140329381)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236089 SCV000294058 uncertain significance not specified 2017-05-15 criteria provided, single submitter clinical testing The I289V variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. The 1000 Genomes Project reports this variant was observed in 1/694 alleles from individuals of Mixed American ancestry, including one hemizygous individual, indicating it may be a rare benign variant in this population. Although the I289V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties, it occurs at a position that is conserved across species. Consequently, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Nevertheless, another pathogenic missense variant in the same residue (I289F) has been reported in the Human Gene Mutation Database in association with Fabry disease (Stenson et al., 2014).
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000236089 SCV000539243 uncertain significance not specified 2017-01-24 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: This variant has been seen in one patient with Fabry disease. It is present in ExAC with a Max MAF of 0.11% in Latino chrs (with 2 hemizygotes). It's been seen in 1 female with symptoms of Fabry disease. It is classified in ClinVar with 1 star as VUS by GeneDx and Albrecht-Kossel-Institute,Medical University Rostock.
Invitae RCV000859613 SCV000622194 likely benign not provided 2018-12-12 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000209743 SCV000803618 benign Fabry disease 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Benign, for Fabry disease, in X-linked Recessive manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS3 => Well-established in vitro or in vivo functional studies show no damaging effect on protein function or splicing (PMID:26415523).
Albrecht-Kossel-Institute,Medical University Rostock RCV000209743 SCV000246077 uncertain significance Fabry disease 2014-01-01 no assertion criteria provided research
Albrecht-Kossel-Institute,Medical University Rostock RCV000209181 SCV000246078 drug response Deoxygalactonojirimycin response 2014-01-01 no assertion criteria provided research

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