ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.1061T>A (p.Ile354Lys)

dbSNP: rs1928135337
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001280904 SCV004357515 pathogenic Fabry disease 2023-02-09 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with lysine at codon 354 of the GLA protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over ten male and female individuals affected with Fabry disease (PMID: 15086478, 18784903, 25666440, 25949379, 25965380, 28672034, 28717668, 30386727), and in three asymptomatic female individuals (PMID: 18784903). It has been shown that this variant segregates with disease in 4 affected males and 9 symptomatic females in one family (PMID: 28717668). Leukocyte or serum GLA enzyme activities were reported to be barely detectable in affected male carriers (PMID: 18057066, 18784903, 28717668). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.
All of Us Research Program, National Institutes of Health RCV001280904 SCV004820601 pathogenic Fabry disease 2023-04-10 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with lysine at codon 354 of the GLA protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in over ten male and female individuals affected with Fabry disease (PMID: 15086478, 18784903, 25666440, 25949379, 25965380, 28672034, 28717668, 30386727), and in three asymptomatic female individuals (PMID: 18784903). It has been shown that this variant segregates with disease in 4 affected males and 9 symptomatic females in one family (PMID: 28717668). Leukocyte or serum GLA enzyme activities were reported to be barely detectable in affected male carriers (PMID: 18057066, 18784903, 28717668). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Based on the available evidence, this variant is classified as Pathogenic.
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare RCV001280904 SCV001468250 pathogenic Fabry disease 2020-03-24 no assertion criteria provided clinical testing

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