ClinVar Miner

Submissions for variant NM_130838.3(UBE3A):c.1516C>T (p.Arg506Cys) (rs1064793307)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478539 SCV000565710 pathogenic not provided 2017-03-17 criteria provided, single submitter clinical testing The R506C variant in the UBE3A gene has been reported previously in association with Angelman syndrome (Baumer et al., 1999; Camprubi et al., 2009; Carvill et al., 2013; Yi et al., 2015). The R506C variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R506C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R506C as a pathogenic variant.
Invitae RCV000690582 SCV000818272 likely pathogenic Angelman syndrome 2018-07-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 506 of the UBE3A protein (p.Arg506Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with Angelman syndrome (PMID: 26255772). This variant has also been reported to be maternally inherited in an unrelated individual affected with Angelman syndrome (PMID: 19213023). ClinVar contains an entry for this variant (Variation ID: 418572). Experimental studies have shown that this missense change results in reduced UBE3A protein expression (PMID: 26255772). 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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