Submissions for variant NM_001042492.3(NF1):c.5327C>G (p.Ser1776Ter)

dbSNP: rs2069376973

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001233467	SCV001406064	pathogenic	Neurofibromatosis, type 1	2023-02-26	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 960019). This premature translational stop signal has been observed in individuals with neurofibromatosis type 1 (PMID: 10862084, 16835897, 23758643, 31370276). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1755*) 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).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001233467	SCV001479212	pathogenic	Neurofibromatosis, type 1	2020-10-26	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001233467	SCV002560114	pathogenic	Neurofibromatosis, type 1	2022-03-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002339643	SCV002643370	pathogenic	Hereditary cancer-predisposing syndrome; Cardiovascular phenotype	2024-01-31	criteria provided, single submitter	clinical testing	The c.5264C>G (p.S1755*) alteration, located in coding exon 37 of the NF1 gene, results from a C to G substitution at nucleotide position 5264. This changes the amino acid from a serine (S) to a stop codon at amino acid position 1755. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been detected in several individuals diagnosed with neurofibromatosis type 1 (NF1) (Messiaen, 2000; De Luca, 2004; Lee, 2006; Nemethova, 2013; Giugliano, 2019). Based on the available evidence, this alteration is classified as pathogenic.
GeneDx	RCV004768950	SCV005376830	pathogenic	not provided	2024-04-20	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: 19292874, 25525159, 24789688, 15146469, 10862084, 31370276)
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001233467	SCV005417328	pathogenic	Neurofibromatosis, type 1		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1+PS4_Supporting+PP4+PM6_Supporting
GenomeConnect - Invitae Patient Insights Network	RCV003483801	SCV004228598	not provided	Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 07-09-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.