Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000214387 | SCV000277574 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-07-23 | criteria provided, single submitter | clinical testing | The p.I967V variant (also known as c.2899A>G), located in coding exon 22 of the NF1 gene, results from an A to G substitution at nucleotide position 2899. The isoleucine at codon 967 is replaced by valine, an amino acid with highly 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 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000alleles tested) in our clinical cohort.This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive.Since supporting evidence is limited at this time, the clinical significance of p.I967Vremains unclear. |
| Invitae | RCV000536111 | SCV000628470 | uncertain significance | Neurofibromatosis, type 1 | 2023-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 967 of the NF1 protein (p.Ile967Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 233237). 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. 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. |
| Genome- |
RCV000536111 | SCV002560240 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002485430 | SCV002783074 | uncertain significance | Neurofibromatosis, familial spinal; Juvenile myelomonocytic leukemia; Neurofibromatosis, type 1; Neurofibromatosis-Noonan syndrome; Café-au-lait macules with pulmonary stenosis | 2021-12-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV004558559 | SCV005047675 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-05-26 | criteria provided, single submitter | clinical testing | The c.2899A>G (p.I967V) alteration is located in exon 22 (coding exon 22) of the NF1 gene. This alteration results from a A to G substitution at nucleotide position 2899, causing the isoleucine (I) at amino acid position 967 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |