Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048657 | SCV001212671 | uncertain significance | Neurofibromatosis, type 2 | 2022-01-17 | 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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"). ClinVar contains an entry for this variant (Variation ID: 845567). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 333 of the NF2 protein (p.Gln333His). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. |
Ambry Genetics | RCV002379536 | SCV002688934 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-02 | criteria provided, single submitter | clinical testing | The p.Q333H variant (also known as c.999G>C), located in coding exon 10 of the NF2 gene, results from a G to C substitution at nucleotide position 999. The amino acid change results in glutamine to histidine at codon 333, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 10, which makes it likely to have some effect on normal mRNA splicing. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |