Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000756434 | SCV000884252 | uncertain significance | not provided | 2018-03-16 | criteria provided, single submitter | clinical testing | The NF1 c.7334T>G; p.Val2445Gly variant, to our knowledge, is not reported in the medical literature, in gene-specific databases, or in the ClinVar database. However, ARUP laboratories has detected this variant in an individual with a clinical diagnosis of neurofibromatosis type 1 who also carried a pathogenic variant. This variant is also absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The valine at this position is highly conserved and computational algorithms (PolyPhen-2, SIFT) predict this variant is deleterious. Considering available information, there insufficient evidence to classify this variant with certainty. |
Labcorp Genetics |
RCV001855873 | SCV002303071 | uncertain significance | Neurofibromatosis, type 1 | 2021-02-11 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 618251). This sequence change replaces valine with glycine at codon 2424 of the NF1 protein (p.Val2424Gly). The valine residue is moderately conserved and there is a moderate physicochemical difference between valine and glycine. This variant is not present in population databases (ExAC no frequency). 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. 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. |
Genome- |
RCV001855873 | SCV002561058 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |