Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000059189 | SCV000490665 | pathogenic | not provided | 2021-08-10 | criteria provided, single submitter | clinical testing | Published functional studies support a damaging effect: significant reduction in GTPase activity and mild reduction of interaction with SPRED1 (Thomas 2012, Hirata 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 26635368, 22807134, 31766501, 25486365, 31370276, 27322474, 23447461, 10336779, 10712197, 24803665, 26633542) |
Invitae | RCV000632346 | SCV000753524 | pathogenic | Neurofibromatosis, type 1 | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 1204 of the NF1 protein (p.Arg1204Gly). This variant is present in population databases (rs199474732, gnomAD 0.004%). This missense change has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10336779, 26635368, 27322474; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 68337). 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. Experimental studies have shown that this missense change affects NF1 function (PMID: 22807134). For these reasons, this variant has been classified as Pathogenic. |
Clinical Molecular Genetics Laboratory, |
RCV000632346 | SCV000899247 | pathogenic | Neurofibromatosis, type 1 | 2019-04-25 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002318949 | SCV001182235 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-03-19 | criteria provided, single submitter | clinical testing | The p.R1204G variant (also known as c.3610C>G), located in coding exon 27 of the NF1 gene, results from a C to G substitution at nucleotide position 3610. The arginine at codon 1204 is replaced by glycine, an amino acid with dissimilar properties. This alteration has been identified an individual meeting NF1 diagnostic criteria (Krkljus S et al. Hum. Mutat., 1998;11:411). This variant has also been detected de novo in multiple unrelated individuals with NF1 (Hirata Y et al. J. Biol. Chem., 2016 Feb;291:3124-34). Experimental studies indicate that this variant will disrupt protein function (Thomas L et al. Hum. Mutat., 2012 Dec;33:1687-96). A different alteration at the same amino acid position, p.R1204W, has been identified in an individual meeting NF1 diagnostic criteria (Ars E et al. Hum. Mol. Genet., 2000 Jan;9:237-47). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this variant is classified as a pathogenic mutation. |
Genome Diagnostics Laboratory, |
RCV000632346 | SCV001479235 | pathogenic | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000059189 | SCV001879392 | likely pathogenic | not provided | 2020-09-22 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant has been identified in at least two individuals with clinical features associated with this gene, with one of those appearing to occur de novo. Assessment of experimental evidence suggests this variant results in abnormal protein function. Studies show a reduction in activity of the GAP-related domain of NF1 (PMID: 22807134, 26635368). Computational tools predict that this variant is damaging. |
Genome- |
RCV000632346 | SCV002559975 | likely pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Laboratorio de Genetica e Diagnostico Molecular, |
RCV000632346 | SCV003807283 | pathogenic | Neurofibromatosis, type 1 | 2022-10-07 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PS3 supporting, PS4 strong, PM2 supporting, PM5 moderated, PM6 moderated, PP2 supporting |
Uni |
RCV000059189 | SCV000090718 | not provided | not provided | no assertion provided | not provided | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000059189 | SCV001956904 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000059189 | SCV001967662 | pathogenic | not provided | no assertion criteria provided | clinical testing |