Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000467306 | SCV000542040 | pathogenic | Neurofibromatosis, type 1 | 2024-01-08 | criteria provided, single submitter | clinical testing | This variant, c.3639_3641del, results in the deletion of 1 amino acid(s) of the NF1 protein (p.Met1215del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with neurofibromatosis type 1 (PMID: 10712197, 16835897, 18546366, 26635368). This variant is also known as 3643delATG. ClinVar contains an entry for this variant (Variation ID: 404465). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects NF1 function (PMID: 26635368). For these reasons, this variant has been classified as Pathogenic. |
Genome Diagnostics Laboratory, |
RCV000467306 | SCV001479234 | pathogenic | Neurofibromatosis, type 1 | 2020-10-26 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001562547 | SCV001785327 | pathogenic | not provided | 2022-05-05 | criteria provided, single submitter | clinical testing | In-frame deletion of 1 amino acid in a non-repeat region; Observed in individuals with Neurofibromatosis type 1 (Lee 2006, Pros 2008, Cannon 2018, Hirata 2016); In silico analysis supports a deleterious effect on protein structure/function; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 10712197, 16835897, 26635368, 29415745, 18546366, 25486365, 22807134) |
Genome- |
RCV000467306 | SCV002559976 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Medical Genetics, |
RCV000467306 | SCV002567799 | pathogenic | Neurofibromatosis, type 1 | 2022-08-17 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002451072 | SCV002613728 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-06-02 | criteria provided, single submitter | clinical testing | The c.3639_3641delAAT pathogenic mutation (also known as p.M1215del) is located in coding exon 27 of the NF1 gene. This pathogenic mutation results from an in-frame AAT deletion at nucleotide positions 3639 to 3641. This results in the in-frame deletion of a methionine at codon 1215. This alteration has been reported in several individuals affected with neurofibromatosis type 1 (Fahsold R et al. Am J Hum Genet, 2000 Mar;66:790-818; Lee MJ et al. Hum Mutat, 2006 Aug;27:832; Pros E et al. Hum Mutat, 2008 Sep;29:E173-93; Sabbagh A et al. Hum Mutat, 2013 Nov;34:1510-8; Hirata Y et al. J Biol Chem, 2016 Feb;291:3124-34). Functional studies have also demonstrated that this alteration impairs binding to the EVH1 domain of SPRED1 (Hirata Y et al. J Biol Chem, 2016 Feb;291:3124-34; Dunzendorfer-Matt T et al. Proc Natl Acad Sci U S A, 2016 07;113:7497-502). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |