Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000196926 | SCV000254495 | uncertain significance | Neurofibromatosis, type 1 | 2020-04-19 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 216401). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This sequence change replaces alanine with valine at codon 1197 of the NF1 protein (p.Ala1197Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. |
| Department Of Biochemistry, |
RCV000196926 | SCV003924387 | likely pathogenic | Neurofibromatosis, type 1 | 2023-05-15 | criteria provided, single submitter | research | Sanger sequencing confirmed that this variant was de novo. This variant was absent from the public databases, including the Genome Aggregation Database (gnomAD) v3.1.2 , ToMMo 38KJPN Allele Frequency Panel, and 82 in-house Japanese exome control data. All three variants were evolutionarily highly conserved and predicted to be deleterious by multiple pathogenicity prediction tools. Based on American College of Medical Genetics and Genomics standards and guidelines, the c.3590C>T, p.(Ala1197Val) variant in NF1 was classified as likely pathogenic (PS2, PM2, PP3). |
| Ambry Genetics | RCV004558447 | SCV005047746 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2023-04-18 | criteria provided, single submitter | clinical testing | The p.A1197V variant (also known as c.3590C>T), located in coding exon 27 of the NF1 gene, results from a C to T substitution at nucleotide position 3590. The alanine at codon 1197 is replaced by valine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |