Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Centre for Mendelian Genomics, |
RCV000626643 | SCV000747345 | likely pathogenic | Cafe au lait spots, multiple; Neurofibroma; Abnormality of vision | 2017-01-01 | criteria provided, single submitter | clinical testing | |
Center for Human Genetics, |
RCV000660052 | SCV000782012 | uncertain significance | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000660052 | SCV000962246 | pathogenic | Neurofibromatosis, type 1 | 2022-07-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1391 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7581973, 9003501, 16513807, 22807134, 27322474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. ClinVar contains an entry for this variant (Variation ID: 523345). This missense change has been observed in individual(s) with NF1- Noonan syndrome and neurofibormatosis type 1 (NF1) (PMID: 24789688, 27322474; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 1391 of the NF1 protein (p.Arg1391Thr). |
Ambry Genetics | RCV002319052 | SCV001183675 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-04-17 | criteria provided, single submitter | clinical testing | The p.R1391T variant (also known as c.4172G>C), located in coding exon 31 of the NF1 gene, results from a G to C substitution at nucleotide position 4172. The arginine at codon 1391 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This alteration has been identified in multiple individuals with neurofibromatosis or suspected of having neurofibromatosis (van Minkelen R et al. Clin. Genet., 2014 Apr;85:318-27). (Evans DG et al. EBioMedicine, 2016 May;7:212-20). (Xu W et al. Int. J. Mol. Med., 2014 Jul;34:53-60). Two additional disease-causing mutations, p.R1391G and p.R1391S, have been described in the same codon. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Genome Diagnostics Laboratory, |
RCV000660052 | SCV001479070 | uncertain significance | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing |