Submissions for variant NM_000642.3(AGL):c.4259+2T>C

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	RCV005238573	SCV005886753	likely pathogenic	Glycogen storage disease type III	2025-02-03	criteria provided, single submitter	clinical testing	Variant summary: AGL c.4259+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of AGL function. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250998 control chromosomes. To our knowledge, no occurrence of c.4259+2T>C in individuals affected with Glycogen Storage Disease Type III and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.