Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000564289 | SCV000674148 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-09 | criteria provided, single submitter | clinical testing | The p.R376Q variant (also known as c.1127G>A), located in coding exon 12 of the NF2 gene, results from a G to A substitution at nucleotide position 1127. The arginine at codon 376 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been identified in a cohort of Chinese esophageal cancer patients (Deng J et al. Front Genet, 2019 Feb;10:47). 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. |
Invitae | RCV000792747 | SCV000932063 | uncertain significance | Neurofibromatosis, type 2 | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 376 of the NF2 protein (p.Arg376Gln). 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. This missense change has been observed in individual(s) with esophageal cancer (PMID: 30833958). ClinVar contains an entry for this variant (Variation ID: 485984). 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 not expected to disrupt NF2 protein function with a negative predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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. |
Genome- |
RCV000792747 | SCV002044879 | uncertain significance | Neurofibromatosis, type 2 | 2021-11-07 | criteria provided, single submitter | clinical testing |