ClinVar Miner

Submissions for variant NM_130838.3(UBE3A):c.2503C>T (p.Leu835Phe) (rs587783097)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000144763 SCV000190979 uncertain significance not provided 2013-02-28 criteria provided, single submitter clinical testing .Leu855Phe (CTT>TTT): c.2563 C>T in exon 13 of the UBE3A gene (NM_130839.1) The novel Leu855Phe missense change has not been published as pathogenic, nor has it been reported as a benign polymorphism to our knowledge. An external variant database has not identifiedLeu855Phe in approximately 6,500 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The amino acid substitution is conservative, as Leucine and Phenylalanine are both uncharged, non-polar amino acids. However, it alters a highly conserved position in the HECT domain of the protein where multiple other missense variants have been reported in association with Angelman syndrome, and multiple in silico algorithms predict it may be damaging to protein structure/function. Therefore, based on the currently available information, Leu855Phe is a strong candidate for a pathogenic variant, although the possibility that it is a benign variant cannot be excluded.
Genetic Services Laboratory, University of Chicago RCV000147882 SCV000195366 likely pathogenic Angelman syndrome 2013-02-08 criteria provided, single submitter clinical testing

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