Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000797514 | SCV000937074 | uncertain significance | Neurofibromatosis, type 2 | 2023-01-13 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 643742). This variant has not been reported in the literature in individuals affected with NF2-related conditions. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 5 of the NF2 protein (p.Ile5Met). |
Ambry Genetics | RCV002397595 | SCV002708635 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-07-01 | criteria provided, single submitter | clinical testing | The p.I5M variant (also known as c.15C>G), located in coding exon 1 of the NF2 gene, results from a C to G substitution at nucleotide position 15. The isoleucine at codon 5 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly 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. |