Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001797386 | SCV002038890 | uncertain significance | not provided | 2021-06-14 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) |
| Ambry Genetics | RCV002334698 | SCV002634908 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2024-10-29 | criteria provided, single submitter | clinical testing | The p.V1621I variant (also known as c.4861G>A), located in coding exon 36 of the NF1 gene, results from a G to A substitution at nucleotide position 4861. The valine at codon 1621 is replaced by isoleucine, an amino acid with highly similar properties. This variant has been identified in an individual diagnosed with neurofibromatosis type 1 (Jeong SY et al. J. Korean Med. Sci., 2006 Feb;21:107-12). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV003598058 | SCV004472981 | uncertain significance | Neurofibromatosis, type 1 | 2024-05-06 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1621 of the NF1 protein (p.Val1621Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1328754). 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) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function with a positive predictive value of 80%. 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. |