ClinVar Miner

Submissions for variant NM_130839.5(UBE3A):c.377C>A (p.Thr126Lys) (rs587781241)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, ClinGen RCV000144317 SCV001712021 pathogenic Angelman syndrome 2021-03-26 reviewed by expert panel curation The variant has been reported to segregate in at least five informative meioses (PMID 25212744, internal database) (PP1_Strong). A pathogenic missense variant (p.Thr106Pro) has been previously identified within this codon which indicates that this residue is critical to the function of the protein (PMID 15054837) (PM5). Protein expression analysis in transfected cell lines has shown that this variant reduces protein function (PMID 26255772) PS3_Supporting). The p.Thr106Lys variant has been observed in at least 1 other individual with Angelman syndrome (PMID 25212744) (PS4_Supporting). The p.Thr106Lys variant in UBE3A is absent from gnomAD (PM2_Supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Thr106Lys variant in UBE3A is classified as pathogenic for Angelman syndrome based on the ACMG/AMP criteria (PP1_strong, PM5, PS3_supporting, PS4_supporting, PM2_supporting, PP3).
Genetic Services Laboratory, University of Chicago RCV000144317 SCV000195373 pathogenic Angelman syndrome 2013-02-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV000144317 SCV000172068 likely pathogenic Angelman syndrome 2014-02-14 no assertion criteria provided clinical testing

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