Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000497076 | SCV000960648 | pathogenic | Neurofibromatosis, type 1 | 2023-07-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 431663). This premature translational stop signal has been observed in individual(s) with diagnosis of neurofibromatosis type 1 (PMID: 26458495). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser1875*) 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). |
Ambry Genetics | RCV002319507 | SCV001186333 | pathogenic | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2018-07-05 | criteria provided, single submitter | clinical testing | The p.S1875* pathogenic mutation (also known as c.5624C>G), located in coding exon 38 of the NF1 gene, results from a C to G substitution at nucleotide position 5624. This changes the amino acid from a serine to a stop codon within coding exon 38. De novo occurrence of this mutation has been reported in an individual with suspected neurofibromatosis type 1 (Yao R et al. J. Dermatol., 2016 May;43:537-42). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Genome- |
RCV000497076 | SCV002560140 | pathogenic | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV000497076 | SCV004176409 | pathogenic | Neurofibromatosis, type 1 | 2023-03-01 | criteria provided, single submitter | clinical testing | The stop gained c.5687C>G (p.Ser1896Ter) variant in the NF1 gene has been observed in individual(s) with diagnosis of neurofibromatosis type 1 (Yao, Ruen et al., 2016). This variant is novel in the gnomAD Exomes and 1000 Genomes. It is submitted to ClinVar as Pathogenic. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The nucleotide change c.5687C>G in NF1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic. |
Medical Genetics, |
RCV000497076 | SCV000588807 | pathogenic | Neurofibromatosis, type 1 | 2017-02-02 | no assertion criteria provided | clinical testing |