Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000802183 | SCV000942001 | pathogenic | Neurofibromatosis, type 1 | 2023-10-24 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 21 of the NF1 gene. It does not directly change the encoded amino acid sequence of the NF1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with clinical features of neurofibromatosis type 1 (PMID: 10862084, 27838393; Invitae). In at least one individual the variant was observed to be de novo. This variant is also known as IVS16-6del4. ClinVar contains an entry for this variant (Variation ID: 647632). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Medical Genomics Laboratory, |
RCV000802183 | SCV001167406 | pathogenic | Neurofibromatosis, type 1 | 2020-01-20 | criteria provided, single submitter | clinical testing | |
Institute of Human Genetics, |
RCV000802183 | SCV001250658 | pathogenic | Neurofibromatosis, type 1 | 2020-01-20 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV000802183 | SCV002561809 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002440682 | SCV002752734 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2022-11-10 | criteria provided, single submitter | clinical testing | The c.2851-6_2851-3delCTTT intronic pathogenic mutation, located in intron 21 of the NF1 gene, results from a deletion of 4 nucleotides within intron 21 of the NF1 gene. The variant has been detected in multiple individuals with neurofibromatosis type 1 (Messiaen LM et al. Hum Mutat, 2000;15:541-55; Calì F et al. Eur J Med Genet, 2017 Feb;60:93-99). RNA studies have demonstrated that this alteration results in skipping of exon 22 (Messiaen LM et al. Hum Mutat, 2000;15:541-55; Wimmer K et al. Hum Mutat, 2020 06;41:1145-1156; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
Fulgent Genetics, |
RCV002501077 | SCV002813204 | pathogenic | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-09-16 | criteria provided, single submitter | clinical testing |