Total submissions: 6
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, |
RCV000632333 | SCV000781960 | uncertain significance | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Center of Genomic medicine, |
RCV000632333 | SCV000840424 | pathogenic | Neurofibromatosis, type 1 | 2018-03-26 | criteria provided, single submitter | clinical testing | |
Gene |
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- |
RCV000632333 | SCV004041689 | uncertain significance | Neurofibromatosis, type 1 | 2023-10-09 | no assertion criteria provided | clinical testing |