ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2798T>C (p.Leu933Pro)

dbSNP: rs1555614342
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000632333 SCV000753510 pathogenic Neurofibromatosis, type 1 2023-11-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 933 of the NF1 protein (p.Leu933Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 27716896, 31776437). ClinVar contains an entry for this variant (Variation ID: 527461). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000632333 SCV000781960 uncertain significance Neurofibromatosis, type 1 2016-11-01 criteria provided, single submitter clinical testing
Center of Genomic medicine, Geneva, University Hospital of Geneva RCV000632333 SCV000840424 pathogenic Neurofibromatosis, type 1 2018-03-26 criteria provided, single submitter clinical testing
GeneDx RCV002307567 SCV002601247 likely pathogenic not provided 2022-11-10 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25486365, 2121369, 31776437, 27716896, 29290338)
Ambry Genetics RCV002438657 SCV002747957 likely pathogenic Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2017-06-26 criteria provided, single submitter clinical testing The p.L933P variant (also known as c.2798T>C), located in coding exon 21 of the NF1 gene, results from a T to C substitution at nucleotide position 2798. The leucine at codon 933 is replaced by proline, an amino acid with similar properties. This variant has been detected in two individuals with neurofibromatosis type 1 (Cassiman C et al. Clin. Genet., 2017 Apr;91:529-535; van Minkelen R et al. Clin. Genet., 2014 Apr;85:318-27). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV000632333 SCV004041689 uncertain significance Neurofibromatosis, type 1 2023-10-09 no assertion criteria provided clinical testing

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