ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.5297C>G (p.Ser1766Ter)

dbSNP: rs1555533555
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522875 SCV000617582 pathogenic not provided 2017-06-23 criteria provided, single submitter clinical testing The S1745X nonsense variant in the NF1 gene has been reported previously in association with NeurofibromatosisType 1 (Rodenhiser et al., 1997; Upadhyaya et al., 2008), Watson syndrome (Castle et al., 2003), andencephalocraniocutaneous lipomatosis (ECCL) (Legius et al., 1995). The S1745X variant is not observed in largepopulation cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Thispathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay
Institute of Human Genetics, University of Leipzig Medical Center RCV001262355 SCV001440186 pathogenic Neurofibromatosis, type 1 2019-01-01 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001262355 SCV001479124 pathogenic Neurofibromatosis, type 1 2020-10-26 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV001262355 SCV002073186 likely pathogenic Neurofibromatosis, type 1 criteria provided, single submitter clinical testing The stop gained p.S1745* in NF1 (NM_000267.3) has been reported to ClinVar as Pathogenic but there is no functional studies. The p.S1745* variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. For these reasons, this variant has been classified as Likely Pathogenic.
Genome-Nilou Lab RCV001262355 SCV002560112 pathogenic Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001262355 SCV003441874 pathogenic Neurofibromatosis, type 1 2023-11-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser1745*) 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 individual(s) with clinical features of neurofibromatosis type 1 (PMID: 7643367, 17960768, 19292874, 24232412). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 449426). For these reasons, this variant has been classified as Pathogenic.
Department of Human Genetics, Hannover Medical School RCV001262355 SCV005397901 pathogenic Neurofibromatosis, type 1 2024-11-15 criteria provided, single submitter clinical testing PVS1, PS2_Moderate, PM2_Supporting

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.