Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018199 | SCV004848745 | likely pathogenic | Neurofibromatosis, type 1 | 2022-08-26 | criteria provided, single submitter | clinical testing | The p.Leu1068PhefsX10 variant in NF1 has not been reported in individuals with neurofibromatosis type 1 and has been identified in 6/25606 African chromosomes by gnomAD (https://gnomad.broadinstitute.org). This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1068 and leads to a premature termination codon 10 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the NF1 gene is an established disease mechanism in autosomal dominant neurofibromatosis type 1. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal dominant neurofibromatosis type 1. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |