ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.6819+1G>T

dbSNP: rs1555534964
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Goettingen RCV001800164 SCV002041906 pathogenic Neurofibromatosis, type 1 2021-12-27 criteria provided, single submitter clinical testing The variant c.6756+1G>T (p.?) is located in the donor splice site of intron 44 of the NF1-gene, it affects a canonical splice site and it is not found in the gnomAD database. In silico programs predict a significant impact on NF1-RNA splicing (varSEAK SSP, SpliceSiteFinder-like, MaxEntScan, NNSPLICE and GeneSplicer), which has not been validated by functional studies yet. This variant has already been identified in an individual with Neurofibromatosis, type 1 (PMID: 31766501). ACMG criteria used for classification: PVS1, PM2, PP5.
3billion RCV002283558 SCV002573181 pathogenic Neurofibromatosis-Noonan syndrome 2022-09-01 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site is predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be associated with NF1--related disorder (ClinVar ID: VCV001329856). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Labcorp Genetics (formerly Invitae), Labcorp RCV001800164 SCV004632647 pathogenic Neurofibromatosis, type 1 2023-11-08 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 44 of the NF1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and 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). Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10712197, 31766501). ClinVar contains an entry for this variant (Variation ID: 1329856). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004720941 SCV005328151 pathogenic not provided 2023-05-24 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele 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: 31766501)

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