Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Medical Genomics Laboratory, |
RCV000856626 | SCV000999187 | pathogenic | Neurofibromatosis, type 1 | 2019-06-05 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000856626 | SCV001419883 | uncertain significance | Neurofibromatosis, type 1 | 2019-11-11 | 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. This variant disrupts the p.Lys1423 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 1568247, 11735023, 11857752, 23244495, 16786508, 27322474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported to affect NF1 protein function (PMID: 1587809). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 29618358). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with methionine at codon 1423 of the NF1 protein (p.Lys1423Met). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and methionine. |