Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000802449 | SCV000942281 | pathogenic | Neurofibromatosis, type 1 | 2022-02-10 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 647845). Disruption of the initiator codon has been observed in individual(s) with neurofibromatosis type 1 (PMID: 18041031, 23668869, 23913538). This sequence change affects the initiator methionine of the NF1 mRNA. The next in-frame methionine is located at codon 68. |
Ambry Genetics | RCV002325548 | SCV002626212 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2017-10-09 | criteria provided, single submitter | clinical testing | The p.M1? variant (also known as c.3G>A), located in coding exon 1 of the NF1 gene, results from a G to A substitution at nucleotide position 3. This alters the methionine residue at the initiation codon. This alteration was detected in one individual who meets National Institute of Health Neurofibromatosis Type 1 clinical criteria (Sabbagh A et al. Hum. Mutat., 2013 Nov;34:1510-8). In addition to the clinical data presented in the literature, since sequence variations that modify the initiation codon (ATG) are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame, this alteration is interpreted as a disease-causing mutation. |
Mayo Clinic Laboratories, |
RCV004792492 | SCV005413187 | likely pathogenic | not provided | 2024-05-08 | criteria provided, single submitter | clinical testing | PP4, PP5, PM2_moderate, PVS1_moderate |
NHS Central & South Genomic Laboratory Hub | RCV000802449 | SCV005907183 | pathogenic | Neurofibromatosis, type 1 | 2025-04-09 | criteria provided, single submitter | clinical testing |