ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.265C>T (p.Leu89Phe) (rs1555986305)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000590425 SCV000857059 uncertain significance not provided 2017-09-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590425 SCV000695737 uncertain significance not provided 2016-06-07 criteria provided, single submitter clinical testing Variant summary: The GLA c.265C>T (p.Leu89Phe) variant involves the alteration of a non-conserved nucleotide. 4/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 87749 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV000525086 SCV000622182 likely pathogenic Fabry disease 2017-03-27 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 89 of the GLA protein (p.Leu89Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a GLA-related disease. This variant has been reported in an individual affected with classic Fabry disease and reduced alpha-galactosidase enzyme activity (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change that has been reported in the homozygous and heterozygous state in affected individuals. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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