ClinVar Miner

Submissions for variant NM_001069.3(TUBB2A):c.743C>T (p.Ala248Val) (rs2808001)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202934 SCV000257767 likely benign not specified 2015-04-14 criteria provided, single submitter clinical testing
GeneDx RCV000254754 SCV000321988 pathogenic not provided 2019-01-08 criteria provided, single submitter clinical testing The A248V variant in the TUBB2A gene has been reported previously as a de novo variant with confirmed parentage in two unrelated individuals with TUBB2A-related disorders (Cushion et al., 2014; Rodan et al., 2017). The A248V variant has also been identified as a de novo variant in other individuals with developmental delay and/or seizures tested at GeneDx. The A248V variant is not observed in large population cohorts (Lek et al., 2016). It is a conservative amino acid substitution, and in-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Functional studies of A248V indicate that this variant has a reduced rate ofheterodimer incorporation into the in vitro cytoskeleton network in comparison with wild type-expressing cells (Cushion et al., 2014). Missense variants in nearby residues have been reported inthe Human Gene Mutation Database in individuals with TUBB2A-related disorders (Stenson et al., 2014). Therefore, we interpret A248V as a pathogenic variant.
NeuroMeGen,Hospital Clinico Santiago de Compostela RCV000114959 SCV000693794 likely pathogenic Cortical dysplasia, complex, with other brain malformations 5 2018-01-01 criteria provided, single submitter clinical testing
Mendelics RCV000114959 SCV001137048 benign Cortical dysplasia, complex, with other brain malformations 5 2019-05-28 criteria provided, single submitter clinical testing
Institute of Human Genetics,Klinikum rechts der Isar RCV000114959 SCV001149975 pathogenic Cortical dysplasia, complex, with other brain malformations 5 2019-06-11 criteria provided, single submitter clinical testing
OMIM RCV000114959 SCV000148869 pathogenic Cortical dysplasia, complex, with other brain malformations 5 2014-04-03 no assertion criteria provided literature only

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