ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6674G>A (p.Trp2225Ter)

gnomAD frequency: 0.00001  dbSNP: rs1193716348
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000579375 SCV000680724 pathogenic not provided 2022-12-16 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation and 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: 23913538, 10712197, 29617658, 31370276, 25074460)
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000660099 SCV000782080 likely pathogenic Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV000660099 SCV001479140 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Invitae RCV000660099 SCV001591758 pathogenic Neurofibromatosis, type 1 2020-01-13 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 25074460, 31370276). ClinVar contains an entry for this variant (Variation ID: 488819). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp2204*) in the NF1 gene. It is expected to result in an absent or disrupted protein product.
Revvity Omics, Revvity RCV000579375 SCV002018320 pathogenic not provided 2019-10-10 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000660099 SCV002560198 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV002377200 SCV002667241 pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2017-06-26 criteria provided, single submitter clinical testing The p.W2204* pathogenic mutation (also known as c.6611G>A), located in coding exon 43 of the NF1 gene, results from a G to A substitution at nucleotide position 6611. This changes the amino acid from a tryptophan to a stop codon within coding exon 43. This alteration was reported in 1/279 patients undergoing clinical testing for NF1 (Pasmant E et al. Eur. J. Hum. Genet., 2015 May;23:596-601). In addition to the information presented in the literature, 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.

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