Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Human Genetics, |
RCV000660018 | SCV000781959 | pathogenic | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000660018 | SCV001486888 | pathogenic | Neurofibromatosis, type 1 | 2023-06-03 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 547614). This missense change has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 22190595; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 929 of the NF1 protein (p.Leu929Pro). 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. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002440405 | SCV002751717 | likely pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-03-16 | criteria provided, single submitter | clinical testing | The p.L929P variant (also known as c.2786T>C), located in coding exon 21 of the NF1 gene, results from a T to C substitution at nucleotide position 2786. The leucine at codon 929 is replaced by proline, an amino acid with similar properties. This alteration has been identified in individuals with a clinical diagnosis of neurofibromatosis type 1 (NF1) in the literature (Ribeiro MJ et al. Invest Ophthalmol Vis Sci, 2012 Jan;53:287-93; Violante IR et al. Brain, 2013 Mar;136:918-25) and at another laboratory (personal communication). 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 variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Ce |
RCV003326486 | SCV004033546 | likely pathogenic | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | NF1: PM2, PM6, PS4:Moderate, PP3 |