Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000632488 | SCV000753673 | likely pathogenic | Neurofibromatosis, type 1 | 2019-11-29 | criteria provided, single submitter | clinical testing | 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has been reported in several individuals affected with neurofibromatosis type I (PMID: 22807134, Invitae). ClinVar contains an entry for this variant (Variation ID: 527578). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with aspartic acid at codon 1398 of the NF1 protein (p.Val1398Asp). The valine residue is highly conserved and there is a large physicochemical difference between valine and aspartic acid. |
| Neuberg Centre For Genomic Medicine, |
RCV000632488 | SCV004047654 | likely pathogenic | Neurofibromatosis, type 1 | criteria provided, single submitter | clinical testing | The NF1 c.4256T>A variant has been reported in individual affected with neurofibromatosis type I (Thomas et. al., 2012). 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 laboratory indicates that this missense variant is expected to disrupt NF1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. The p.Val1419Asp variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Likely Pathogenic. The amino acid change p.Val1419Asp in NF1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Val at position 1419 is changed to a Asp changing protein sequence and it might alter its composition and physico-chemical properties. Therefore, this variant has been classified as Likely Pathogenic. |