Submissions for variant NM_001904.4(CTNNB1):c.1420C>T (p.Arg474Ter)

dbSNP: rs1553631860

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV001092247	SCV001248662	pathogenic	not provided	2019-11-01	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Strasbourg University Hospital	RCV001260750	SCV001437842	pathogenic	Intellectual disability	2020-09-10	criteria provided, single submitter	clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV001374918	SCV001572205	pathogenic	Neurodevelopmental disorder	2021-02-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001092247	SCV001585620	pathogenic	not provided	2024-12-03	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg474*) 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 clinical features of CTNNB1-related conditions (PMID: 25326669, 27915094, 28333917). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 559636). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV001092247	SCV001793852	pathogenic	not provided	2022-10-13	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 (gnomAD); This variant is associated with the following publications: (PMID: 28333917, 34758253, 27915094, 25326669, 27479843, 29786110, 31785789, 33004838)
3billion	RCV000677408	SCV002059042	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2023-09-19	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000559636 /PMID: 25326669). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV002286777	SCV002577572	pathogenic	Microcephalic primordial dwarfism, Alazami type	2022-02-28	criteria provided, single submitter	clinical testing	PVS1, PM2, PP3, PP5
MGZ Medical Genetics Center	RCV000677408	SCV002579785	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2021-12-10	criteria provided, single submitter	clinical testing
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV003126902	SCV003803831	pathogenic	Developmental disorder	2022-01-04	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV000677408	SCV003807448	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2022-03-17	criteria provided, single submitter	clinical testing	ACMG classification criteria: PVS1 very strong, PS4 moderated, PM2 moderated, PM6 moderated
Molecular Genetics Lab, CHRU Brest	RCV003883158	SCV004697623	pathogenic	Medulloblastoma; Pilomatrixoma; Ovarian neoplasm; Severe intellectual disability-progressive spastic diplegia syndrome; Hepatocellular carcinoma; Colorectal cancer; Exudative vitreoretinopathy 7		criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, BC Children's and BC Women's Hospitals	RCV000677408	SCV000803712	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome	2018-03-07	no assertion criteria provided	clinical testing
Genomics England Pilot Project, Genomics England	RCV000677408	SCV001760123	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome		no assertion criteria provided	clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000677408	SCV002318925	pathogenic	Severe intellectual disability-progressive spastic diplegia syndrome		no assertion criteria provided	clinical testing