Submissions for variant NM_001042492.3(NF1):c.2887C>T (p.Gln963Ter)

dbSNP: rs876660444

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000219051	SCV000277873	pathogenic	Hereditary cancer-predisposing syndrome	2015-08-18	criteria provided, single submitter	clinical testing	The p.Q963* pathogenic mutation (also known as c.2887C>T), located in coding exon 22 of the NF1 gene, results from a C to T substitution at nucleotide position 2887. This changes the amino acid from a glutamine to a stop codon within coding exon 22. This mutation was reported in an individual who fulfilled NIH consensus criteria for neurofibromatosistype1 (Messiaen LM, et al. Hum. Mutat. 2000;15(6):541-55). In addition to the clinical data presented in the literature, since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000660024	SCV000781966	pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV000660024	SCV001380670	pathogenic	Neurofibromatosis, type 1	2022-05-02	criteria provided, single submitter	clinical testing	This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln963*) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This premature translational stop signal has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10862084). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 233495).
Revvity Omics, Revvity	RCV001782711	SCV002018303	pathogenic	not provided	2019-11-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000660024	SCV002561811	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
DASA	RCV000660024	SCV002588762	pathogenic	Neurofibromatosis, type 1	2022-11-03	criteria provided, single submitter	clinical testing	The c.2887C>T;p.(Gln963*) variant creates a premature translational stop signal in the NF1 gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 233495; PMID: 10862084; 31370276) - PS4. This variant is not present in population databases (rs876660444, gnomAD; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2. In summary, the currently available evidence indicates that the variant is pathogenic.
Laboratory for Genotyping Development, RIKEN	RCV003165575	SCV002758180	pathogenic	Gastric cancer	2021-07-01	no assertion criteria provided	research
Laboratory of Urology, Hospital Clinic de Barcelona	RCV003332148	SCV004040617	pathogenic	Malignant tumor of urinary bladder		no assertion criteria provided	research