Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001034792 | SCV001198091 | uncertain significance | Neurofibromatosis, type 1 | 2022-10-25 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 834162). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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"). This missense change has been observed in individual(s) with clinical features of neurofibromatosis-Noonan syndrome (PMID: 31370276). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 548 of the NF1 protein (p.Ala548Ser). |
| Gene |
RCV001585932 | SCV001818338 | uncertain significance | not provided | 2020-03-03 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); 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; This variant is associated with the following publications: (PMID: 31370276) |
| Genome- |
RCV001034792 | SCV002561932 | uncertain significance | Neurofibromatosis, type 1 | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002400209 | SCV002704594 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2021-08-24 | criteria provided, single submitter | clinical testing | The p.A548S variant (also known as c.1642G>T), located in coding exon 15 of the NF1 gene, results from a G to T substitution at nucleotide position 1642. This variant impacts the first base pair of coding exon 15. The alanine at codon 548 is replaced by serine, an amino acid with similar properties. This alteration was identified in a individual with cafe au lait macules and an affected first-degree relative (Giugliano T et al. Genes (Basel), 2019 07;10:). 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 this alteration remains unclear. |