Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000702763 | SCV000831631 | uncertain significance | not provided | 2019-06-19 | criteria provided, single submitter | clinical testing | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant has not been reported in the literature in individuals with NEXMIF-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 788 of the KIAA2022 protein (p.Leu788Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |
| New York Genome Center | RCV002265864 | SCV002548787 | uncertain significance | X-linked intellectual disability, Cantagrel type | 2021-09-10 | criteria provided, single submitter | clinical testing | The c.2363T>C, p.Leu788Pro missense variant identified in NEXMIF has not been reported in the literature. This variant has one heterozygous allele in the gnomAD v3.1.1 database suggesting it is not a common benign variant in the populations represented in this database. In silico tools predict a conflicting effect of pathogenicity. Based on the available evidence, the missense variant c.2363T>C, p.Leu788Pro in the NEXMIF gene is classified as a Variant of Uncertain Significance. |