Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001224602 | SCV001396813 | uncertain significance | Neurofibromatosis, type 2 | 2023-06-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 376 of the NF2 protein (p.Arg376Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on NF2 protein function. ClinVar contains an entry for this variant (Variation ID: 952483). This variant has not been reported in the literature in individuals affected with NF2-related conditions. |
Ambry Genetics | RCV002447128 | SCV002754082 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-21 | criteria provided, single submitter | clinical testing | The p.R376W variant (also known as c.1126C>T), located in coding exon 12 of the NF2 gene, results from a C to T substitution at nucleotide position 1126. The arginine at codon 376 is replaced by tryptophan, an amino acid with dissimilar properties. 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. |