ClinVar Miner

Submissions for variant NM_130839.5(UBE3A):c.2096A>C (p.Lys699Thr)

gnomAD frequency: 0.00007  dbSNP: rs202161423
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Total submissions: 6
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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 RCV000144356 SCV004176025 benign Angelman syndrome 2023-12-06 reviewed by expert panel curation The allele frequency of The p.Lys679Thr variant in UBE3A (NM_130838.2) is 0.03187% in European (non-Finnish) sub population in gnomAD v4, which is high enough to be classified as benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BA1). The p.Lys679Thr variant is found in a patient with an alternate molecular basis of disease (internal database - Baylor) (BP5). In summary, the p.Lys679Thr variant in UBE3A (NM_130838.2) is classified as benign based on the ACMG/AMP criteria (BA1, BP5).
GeneDx RCV000766996 SCV000191057 likely benign not provided 2021-02-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25212744)
Genetic Services Laboratory, University of Chicago RCV000192972 SCV000249351 uncertain significance not specified 2015-02-12 criteria provided, single submitter clinical testing
Invitae RCV000144356 SCV000952986 uncertain significance Angelman syndrome 2024-01-02 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 679 of the UBE3A protein (p.Lys679Thr). This variant is present in population databases (rs202161423, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with UBE3A-related conditions. ClinVar contains an entry for this variant (Variation ID: 156144). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on UBE3A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen RCV000766996 SCV004131435 uncertain significance not provided 2023-08-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000144356 SCV000188533 uncertain significance Angelman syndrome 2014-02-14 no assertion criteria provided clinical testing possible diagnosis of Angelman syndrome

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