ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.758T>C (p.Ile253Thr) (rs727505292)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000156824 SCV000206545 uncertain significance not specified 2014-09-25 criteria provided, single submitter clinical testing The Ile253Thr variant in GLA has been reported in 1 male with Fabry disease (Sco tt 2013). It was absent from large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Ile253Thr va riant is uncertain.
Invitae RCV000209022 SCV001403441 likely pathogenic Fabry disease 2019-10-18 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 253 of the GLA protein (p.Ile253Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with clinical features of Fabry disease (PMID: 27896103, 23465405, Invitae). ClinVar contains an entry for this variant (Variation ID: 180021). This variant has been reported to affect GLA protein function (PMID: 27657681). This variant disrupts the p.Ile253 amino acid residue in GLA. Other variant(s) that disrupt this residue have been observed in individuals with GLA-related conditions (PMID: 23935525, 27657681), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Albrecht-Kossel-Institute,Medical University Rostock RCV000209022 SCV000246069 pathogenic Fabry disease 2014-01-01 no assertion criteria provided research
Albrecht-Kossel-Institute,Medical University Rostock RCV000209285 SCV000246070 drug response Deoxygalactonojirimycin response 2014-01-01 no assertion criteria provided research

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