Submissions for variant NM_001042492.3(NF1):c.943C>T (p.Gln315Ter)

dbSNP: rs766011053

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659970	SCV000781884	pathogenic	Neurofibromatosis, type 1	2016-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000659970	SCV001233444	pathogenic	Neurofibromatosis, type 1	2021-08-28	criteria provided, single submitter	clinical testing	Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 547574). This sequence change creates a premature translational stop signal (p.Gln315*) 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 variant is not present in population databases (ExAC no frequency). This premature translational stop signal has been observed in individual(s) with neurofibromatosis, type 1 (PMID: 10874316).
GeneDx	RCV001584518	SCV001812608	pathogenic	not provided	2024-11-22	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; Published functional studies demonstrate a damaging effect: aberrant splicing with skipping of exon 9 (also published as exon 7) (PMID: 26509978, 15523642); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 17981615, 25525159, 15523642, 19339519, 26509978, 10874316)
Genome-Nilou Lab	RCV000659970	SCV002561613	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004993918	SCV005454602	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2024-11-21	criteria provided, single submitter	clinical testing	The p.Q315* pathogenic mutation (also known as c.943C>T), located in coding exon 9 of the NF1 gene, results from a C to T substitution at nucleotide position 943. This changes the amino acid from a glutamine to a stop codon within coding exon 9. This variant was reported in multiple individuals with features consistent with Neurofibromatosis type 1 (NF1) (Wimmer K et al. Hum Mutat, 2000 Jul;16:90-1; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Department of Pediatrics, Taizhou Central Hospital, Taizhou University Hospital	RCV004556064	SCV005045320	pathogenic	Neurofibromatosis-Noonan syndrome	2024-02-01	no assertion criteria provided	clinical testing