Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000200386 | SCV000253824 | pathogenic | Neurofibromatosis, type 1 | 2023-06-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 23 and introduces a premature termination codon (PMID: 7633431, 10607834, 12807981). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 216062). This variant is also known as IVS18+1G>T. Disruption of this splice site has been observed in individual(s) with neurofibromatosis type 1 (PMID: 10607834, 12807981, 16944272, 18546366). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 23 of the NF1 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. |
| Genomic Research Center, |
RCV000200386 | SCV001251913 | pathogenic | Neurofibromatosis, type 1 | 2020-05-03 | criteria provided, single submitter | clinical testing | |
| Genetics and Molecular Pathology, |
RCV000200386 | SCV002556381 | pathogenic | Neurofibromatosis, type 1 | 2021-10-29 | criteria provided, single submitter | clinical testing | The NF1 c.3113+1G>T variant is classified as Pathogenic (PVS1_Moderate, PS4_Moderate, PM2) |
| Genome- |
RCV000200386 | SCV002559927 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002321796 | SCV002607900 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-10-22 | criteria provided, single submitter | clinical testing | The c.3113+1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide after coding exon 23 of the NF1 gene. This mutation has been detected in multiple individuals who fulfilled diagnostic criteria for neurofibromatosis type 1 or with features of NF1 (Griffiths S et al. Fam Cancer, 2007;6:21-34; Sabbagh A et al. Hum Mutat, 2013 Nov;34:1510-8; Kang E et al. J Hum Genet, 2020 Jan;65:79-89). RNA studies have demonstrated that the alteration results in skipping of exon 23, leading to an in-frame deletion in a region critical to protein function (Ars E et al. J Med Genet, 2003 Jun;40:e82). Another alteration impacting the same donor site (c.3113+1G>A) has been detected in NF1 patients and has been shown to result in skipping of exon 23 by RNA studies (Upadhyaya M et al. Hum. Mutat., 2008 Aug;29:E103-11; Thomas L et al. Eur. J. Hum. Genet., 2012 Apr;20:411-9; Emmerich D et al. Eur. J. Hum. Genet., 2015 Jun;23:870-3; Hutter S et al. Hum. Genet., 2016 May;135:469-75; Purandare SM et al. Hum. Mol. Genet., 1995 Apr;4:767-8; Ars E et al. J. Med. Genet., 2003 Jun;40:e82; Pros E et al. Hum. Mutat., 2008 Sep;29:E173-93; Ambry internal data). The c.3113+1G>T variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV004567410 | SCV005052211 | pathogenic | Juvenile myelomonocytic leukemia | 2024-02-25 | criteria provided, single submitter | clinical testing |