Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002445179 | SCV001189620 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2019-02-06 | criteria provided, single submitter | clinical testing | The p.S2684G variant (also known as c.8050A>G), located in coding exon 54 of the NF1 gene, results from an A to G substitution at nucleotide position 8050. The amino acid change results in serine to glycine at codon 2684, an amino acid with similar properties. This change occurs in the last base pair of coding exon 54; however, in silico models do not predict a deleterious effect on mRNA splicing. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV002552422 | SCV003471628 | uncertain significance | Neurofibromatosis, type 1 | 2022-10-22 | criteria provided, single submitter | clinical testing | 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 827421). This variant has not been reported in the literature in individuals affected with NF1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 2684 of the NF1 protein (p.Ser2684Gly). |