Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000632633 | SCV000753818 | uncertain significance | Neurofibromatosis, type 2 | 2023-11-18 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 66 of the NF2 protein (p.Tyr66Asn). This variant is present in population databases (rs772274240, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 527688). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF2 protein function with a positive predictive value of 80%. 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. |
Ambry Genetics | RCV001013893 | SCV001174532 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-09 | criteria provided, single submitter | clinical testing | The p.Y66N variant (also known as c.196T>A), located in coding exon 2 of the NF2 gene, results from a T to A substitution at nucleotide position 196. The tyrosine at codon 66 is replaced by asparagine, an amino acid with dissimilar properties. This alteration was identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS One, 2018 Apr;13:e0194098). 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. |
Genome- |
RCV000632633 | SCV002044838 | uncertain significance | Neurofibromatosis, type 2 | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003156268 | SCV003845599 | uncertain significance | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in any cases, but was observed in unaffected controls from a melanoma study (Pritchard et al., 2018); This variant is associated with the following publications: (PMID: 11756419, 16324214, 29641532) |