Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130170 | SCV000185006 | uncertain significance | Hereditary cancer-predisposing syndrome | 2015-10-22 | criteria provided, single submitter | clinical testing | The p.R1337W variant (also known as c.4009C>T), located in coding exon 30 of the NF1 gene, results from a C to T substitution at nucleotide position 4009. The arginine at codon 1337 is replaced by tryptophan, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs146306756. Based on data from the NHLBI Exome Sequencing Project (ESP), the T-allele has an overall frequency of approximately 0.01% (1/13006), having been observed in 0% (0/4406) of African American alleles, and in 0.01% (1/8600) of European American alleles.This variant was not reported in the 1000 Genomes Project population-based cohort.To date, this alteration has been detected with an allele frequency of approximately 0.004% (greater than 110000 alleles tested) in our clinical cohort. Based on protein sequence alignment, thisamino acid position is well 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 ofp.R1337Wremains unclear. |
Invitae | RCV000198849 | SCV000254499 | uncertain significance | Neurofibromatosis, type 1 | 2024-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1337 of the NF1 protein (p.Arg1337Trp). This variant is present in population databases (rs146306756, gnomAD 0.01%). This missense change has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 30262796). ClinVar contains an entry for this variant (Variation ID: 141586). 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. |
Mendelics | RCV000198849 | SCV000839145 | uncertain significance | Neurofibromatosis, type 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000130170 | SCV002527549 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-03 | criteria provided, single submitter | curation | |
Genome- |
RCV000198849 | SCV002560360 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing |