Submissions for variant NM_000169.3(GLA):c.723dup (p.Ile242fs)

dbSNP: rs869312391

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192397	SCV001360483	pathogenic	Fabry disease	2019-01-29	criteria provided, single submitter	clinical testing	Variant summary: GLA c.723dupT (p.Ile242TyrfsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (eg. c.735G>A (p.Trp245X), c.748C>T (p.Gln250X), and c.830G>A (p.Trp277X)). The variant was absent in 87762 control chromosomes (ExAC). c.723dupT has been reported in the literature in individuals affected with Fabry Disease (Burlina_2008, Kitani_2019, Lenders_2018, Sakurab_2018). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Lenders_2018). These data indicate that the variant is likely to be associated with disease. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.