Submissions for variant NM_001904.4(CTNNB1):c.1603C>T (p.Arg535Ter)

dbSNP: rs886039332

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000255131	SCV000321527	pathogenic	not provided	2021-10-22	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 25533962, 27915094, 31309540, 28135719, 30952489, 28191890, 26350204, 33425807, 31031587, 32334381, 31785789)
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV000495849	SCV000994578	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2018-12-05	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV001260751	SCV001437843	pathogenic	Intellectual disability	2020-09-10	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001335878	SCV001529131	pathogenic	Exudative vitreoretinopathy 7	2018-05-18	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as de novo in at least two patients with syndromic developmental disorder [PMID 26350204, 27915094]
Laboratory of Human Genetics, Universidade de São Paulo	RCV000495849	SCV002506519	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2022-03-16	criteria provided, single submitter	research	This variant meets our criteria to be classified as pathogenic based upon segregation studies, absence from controls, and in-silico evaluation of pathogenicity.
Invitae	RCV000255131	SCV004292681	pathogenic	not provided	2023-10-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg535*) in the CTNNB1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTNNB1 are known to be pathogenic (PMID: 23033978, 24614104, 25326669, 26350204, 28575650). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with CTNNB1-related conditions (PMID: 26350204, 27915094). ClinVar contains an entry for this variant (Variation ID: 265085). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000495849	SCV000583592	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2019-03-18	no assertion criteria provided	literature only
Stankiewicz Research Laboratory, Baylor College of Medicine	RCV000984346	SCV001055846	likely pathogenic	Abnormal lung growth, pulmonary hypertension, microcephaly, and spasticity	2019-10-01	no assertion criteria provided	research
GenomeConnect - Simons Searchlight	RCV000495849	SCV001443351	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2017-02-06	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-02-06 and interpreted as Pathogenic. Variant was initially reported on 2014-10-27 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.