Submissions for variant NM_015559.3(SETBP1):c.1765C>T (p.Arg589Ter)

dbSNP: rs1568235086

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000760784	SCV000890679	pathogenic	not provided	2024-11-10	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: 28487787, 33391157, 33907317, 33057194, 37010288, 35982159)
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000760784	SCV001905588	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000760784	SCV003315167	pathogenic	not provided	2022-09-27	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 620410). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with intellectual disability (PMID: 33391157). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg589*) in the SETBP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SETBP1 are known to be pathogenic (PMID: 21037274, 25217958).
Ambry Genetics	RCV004027175	SCV004946254	pathogenic	Inborn genetic diseases	2023-10-10	criteria provided, single submitter	clinical testing	The c.1765C>T (p.R589*) alteration, located in exon 4 (coding exon 3) of the SETBP1 gene, consists of a C to T substitution at nucleotide position 1765. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 589. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay._x000D_ _x000D_ for SETBP1-related neurodevelopmental disorder; however, its clinical significance for Schinzel-Giedion syndrome is uncertain. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been reported in multiple individuals with features consistent with SETBP1-related neurodevelopmental disorder including one de novo occurrence (Leonardi, 2020; Morgan, 2021). Based on the available evidence, this alteration is classified as pathogenic.
GenomeConnect - Simons Searchlight	RCV001265285	SCV001443402	likely pathogenic	Intellectual disability, autosomal dominant 29	2017-11-17	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-11-17 and interpreted as Likely Pathogenic. Variant was initially reported on 2015-05-13 by GTR ID of laboratory name North East Thames Genetic Service. The reporting laboratory might also submit to ClinVar.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000760784	SCV001743546	pathogenic	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000760784	SCV001809387	pathogenic	not provided		no assertion criteria provided	clinical testing
GenomeConnect - Brain Gene Registry	RCV001816816	SCV002064263	not provided	Schinzel-Giedion syndrome; Intellectual disability, autosomal dominant 29		no assertion provided	phenotyping only	Variant reported in multiple GenomeConnect participants by GeneDx. Variant interpreted as Pathogenic and reported, most recently, on 04-29-2020 as well as on 11-14-2018. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.