Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660136 | SCV000782130 | pathogenic | Neurofibromatosis, type 2 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001567642 | SCV001791365 | likely pathogenic | not provided | 2019-12-16 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect: fails to bind Lats1 and results in decreased phosphor-YAP (Li et al., 2015); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 16983642, 26045165) |
Genome- |
RCV000660136 | SCV002045428 | likely pathogenic | Neurofibromatosis, type 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002397341 | SCV002707460 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-01-27 | criteria provided, single submitter | clinical testing | The p.L517P variant (also known as c.1550T>C), located in coding exon 14 of the NF2 gene, results from a T to C substitution at nucleotide position 1550. The leucine at codon 517 is replaced by proline, an amino acid with similar properties. This alteration was seen in a patient with bilateral vestibular schwannomas (Ahronowitz I et al. Hum. Mutat., 2007 Jan;28:1-12). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Invitae | RCV000660136 | SCV003250441 | uncertain significance | Neurofibromatosis, type 2 | 2022-04-28 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 547709). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects NF2 function (PMID: 26045165). 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 variant has not been reported in the literature in individuals affected with NF2-related conditions. This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 517 of the NF2 protein (p.Leu517Pro). This variant is not present in population databases (gnomAD no frequency). |