Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000991192 | SCV001209213 | uncertain significance | Neurofibromatosis, type 1 | 2019-12-25 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with NF1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with phenylalanine at codon 1829 of the NF1 protein (p.Val1829Phe). The valine residue is moderately conserved and there is a small physicochemical difference between valine and phenylalanine. |
| Gene |
RCV003226990 | SCV003923616 | uncertain significance | not provided | 2022-11-03 | 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; Has not been previously published as pathogenic or benign to our knowledge |
| Swedish Neurofibromatosis Center, |
RCV000991192 | SCV001132746 | likely pathogenic | Neurofibromatosis, type 1 | 2019-12-17 | no assertion criteria provided | clinical testing | PM1: Hot-spot of length 61 base-pairs has 16 non-VUS variants PM2: Variant not found in GnomAD exomes PP2: 204 out of 225 non-VUS missense variants in gene NF1 are pathogenic PP#: Pathogenic computational verdict because 11 pathogenic predictions |