Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000219194 | SCV000273459 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-01-16 | criteria provided, single submitter | clinical testing | The p.N78K variant (also known as c.234T>A), located in coding exon 3 of the NF1 gene, results from a T to A substitution at nucleotide position 234. The asparagine at codon 78 is replaced by lysine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 30000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be benign and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.N78K remains unclear. |
Labcorp Genetics |
RCV000227890 | SCV000284409 | uncertain significance | Neurofibromatosis, type 1 | 2022-12-03 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 230049). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is present in population databases (no rsID available, gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 78 of the NF1 protein (p.Asn78Lys). |
Gene |
RCV001753656 | SCV002005336 | uncertain significance | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV000227890 | SCV002561425 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002494585 | SCV002785303 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-08-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004558481 | SCV005047622 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-01-31 | criteria provided, single submitter | clinical testing | The c.234T>A (p.N78K) alteration is located in exon 3 (coding exon 3) of the NF1 gene. This alteration results from a T to A substitution at nucleotide position 234, causing the asparagine (N) at amino acid position 78 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |