ClinVar Miner

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

dbSNP: rs2069376973
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001233467 SCV001406064 pathogenic Neurofibromatosis, type 1 2023-02-26 criteria provided, single submitter clinical testing 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with neurofibromatosis type 1 (PMID: 10862084, 16835897, 23758643, 31370276). ClinVar contains an entry for this variant (Variation ID: 960019). For these reasons, this variant has been classified as Pathogenic.
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 2020-03-17 criteria provided, single submitter clinical testing The p.S1755* pathogenic mutation (also known as c.5264C>G), 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 to a stop codon within coding exon 37. This mutation has been detected in several Neurofibromatosis type 1 (NF1) cohorts, some of which fulfilled NIH diagnostic criteria (Nemethova M et al. Ann. Hum. Genet., 2013 Sep;77:364-79; Messiaen LM et al. Hum. Mutat., 2000;15:541-55; De Luca A et al. Hum. Mutat., 2004 Jun;23:629; Lee MJ et al. Hum. Mutat., 2006 Aug;27:832). 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.
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.

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