Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000555970 | SCV000628586 | pathogenic | Neurofibromatosis, type 1 | 2018-02-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with isoleucine at codon 1430 of the NF1 protein (p.Asn1430Ile). The asparagine residue is moderately conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in an individual affected with neurofibromatosis type 1 (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Another missense substitution at this codon (p.Asn1430Asp) has been reported in individuals affected with neurofibromatosis type 1 (PMID: 21567923, 27322474). For these reasons, this variant has been classified as Pathogenic. |
Center for Human Genetics, |
RCV000555970 | SCV000782020 | uncertain significance | Neurofibromatosis, type 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002286749 | SCV002576996 | likely pathogenic | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25486365, 22807134) |