Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001207293 | SCV001378638 | uncertain significance | Neurofibromatosis, type 1 | 2019-08-26 | 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 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: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 1029 of the NF1 protein (p.Leu1029Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. |
Ambry Genetics | RCV002322016 | SCV002608896 | uncertain significance | Hereditary cancer-predisposing syndrome; Cardiovascular phenotype | 2020-09-30 | criteria provided, single submitter | clinical testing | The p.L1029P variant (also known as c.3086T>C), located in coding exon 23 of the NF1 gene, results from a T to C substitution at nucleotide position 3086. The leucine at codon 1029 is replaced by proline, 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. |