ClinVar Miner

Submissions for variant NM_000169.2(GLA):c.605G>A (p.Cys202Tyr) (rs869312344)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000726225 SCV000343037 pathogenic not provided 2018-04-02 criteria provided, single submitter clinical testing
Invitae RCV000359005 SCV000748693 likely pathogenic Fabry disease 2018-01-11 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 202 of the GLA protein (p.Cys202Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Fabry disease including an individual with no detectable GLA enzyme activity, a finding that is highly specific for this condition (PMID: 9100224, 23935525, 19387866). ClinVar contains an entry for this variant (Variation ID: 222314). Experimental studies have shown that this missense change abrogates GLA enzyme activity (PMID: 26415523). A different missense substitution at this codon (p.Cys202Trp) has been reported in an individual affected with Fabry disease (PMID: 10208848). 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.

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