Submissions for variant NM_001904.4(CTNNB1):c.1925_1926del (p.Glu642fs)

dbSNP: rs1553632361

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598918	SCV000709956	pathogenic	not provided	2022-07-28	criteria provided, single submitter	clinical testing	Frameshift 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 (gnomAD); This variant is associated with the following publications: (PMID: 25326669, 26845106, 28191889, 33004838, 33994118)
Ambry Genetics	RCV000624274	SCV000742817	pathogenic	Inborn genetic diseases	2017-07-31	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000598918	SCV001450327	pathogenic	not provided	2016-10-14	criteria provided, single submitter	clinical testing
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV000598918	SCV001468959	pathogenic	not provided		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000598918	SCV001580867	pathogenic	not provided	2024-07-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu642Valfs*5) 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 microcephaly, developmental delay, intellectual disability, and severe hypotonia (PMID: 25326669, 26845106). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 503703). For these reasons, this variant has been classified as Pathogenic.
New York Genome Center	RCV001265236	SCV001761163	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2020-07-03	criteria provided, single submitter	clinical testing	The de novo c.1925_1926del (p.Glu642ValfsTer5) variant identified in the CTNNB1 gene is the deletion of two nucleotides resulting in a frameshift of the protein at amino acid 642/782 (exon 12/15), and is predicted to lead to the premature termination of the protein 5 amino acids downstream. This variant is absent from gnomAD(v3.0) suggesting it is not a common benign variant in the populations represented in that database. This variant is reported in ClinVar as Pathogenic (VarID:503703) and has been reported in multiple affected individuals in the literature [PMID:25326669,PMID:26845106]. Given its deleterious nature, presence de novo in this individual, absence in population databases, and observation in multiple affected individuals in the literature, the c.1925_1926del (p.Glu642ValfsTer5) variant identified in the CTNNB1 gene is reported as Pathogenic.
Neurometabolic Diseases Laboratory, Bellvitge Biomedical Research Institute (IDIBELL)	RCV001265236	SCV003920753	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2023-04-27	criteria provided, single submitter	research
GenomeConnect - Simons Searchlight	RCV001265236	SCV001443348	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2018-12-10	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-12-10 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.