Submission Details

CTNNB1 was first reported in relation to autosomal dominant CTNNB1-related severe intellectual disability-progressive spastic diplegia syndrom in 2012 (23033978: de Ligt et al. 2012). At least six unique loss of function variants have been reported in humans. Evidence supporting this gene-disease relationship includes case-level and experimental data. Variants in this gene have been reported in at least six probands from three publications (23033978: de Ligt et al. 2012; 25326669: Kuechler et al. 2015; 27915094: Kharbanda et al. 2017). Only de novo variants have been reported in literature. More evidence is available in the literature, but the maximum score for genetic evidence has been reached (12 pts.). The mechanism for disease is haploinsufficiency. This gene-disease association is supported by an animal model and in vitro functional assays (24614104: Tucci et al. 2014). In summary, there is strong evidence to support the relationship between CTNNB1 and CTNNB1-related severe intellectual disability-progressive spastic diplegia syndrome (autosomal dominant). Additional experimental evidence is required to reach a definitive classification.

PubMed IDs:

23033978 25326669 27915094 24614104

Assertion Criteria:

Click here to view assertion criteria

https://www.clinicalgenome.org/site/assets/files/3975/gene-disease_validity_standard_operating_procedures_version_7-1.pdf

Submitter Submitted Date:

10/15/2020

The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).

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