Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001963891 | SCV002249262 | uncertain significance | Neurofibromatosis, type 2 | 2022-08-09 | 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1466141). 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 lysine, which is basic and polar, with glutamine, which is neutral and polar, at codon 17 of the NF2 protein (p.Lys17Gln). |
Ambry Genetics | RCV002334985 | SCV002642373 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-29 | criteria provided, single submitter | clinical testing | The p.K17Q variant (also known as c.49A>C), located in coding exon 1 of the NF2 gene, results from an A to C substitution at nucleotide position 49. The lysine at codon 17 is replaced by glutamine, an amino acid with similar 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. |
All of Us Research Program, |
RCV001963891 | SCV004832561 | uncertain significance | Neurofibromatosis, type 2 | 2023-06-26 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamine at codon 17 of the NF2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with NF2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |