Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000486304 | SCV000573968 | pathogenic | not provided | 2017-09-28 | criteria provided, single submitter | clinical testing | The c.1973_1974delTC variant in the NF1 gene causes a frameshift starting with codon Leucine 658, changes this amino acid to a Proline residue and creates a premature Stop codon at position 11 of the new reading frame, denoted p.Leu658ProfsX11. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although this variant has not been previously reported to our knowledge, we consider it to be pathogenic. |
Labcorp Genetics |
RCV003597976 | SCV004376876 | pathogenic | Neurofibromatosis, type 1 | 2023-11-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu658Profs*11) in the NF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 424182). For these reasons, this variant has been classified as Pathogenic. |