Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostics Laboratory, |
RCV000761242 | SCV000891198 | likely pathogenic | Intellectual disability, X-linked 1 | 2017-02-24 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000761242 | SCV001203204 | pathogenic | Intellectual disability, X-linked 1 | 2020-03-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the IQSEC2 protein. Other variant(s) that disrupt this region (p.Ala1347Glyfs*40) have been determined to be pathogenic (PMID: 27864847). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with IQSEC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 623140). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change results in a premature translational stop signal in the IQSEC2 gene (p.Pro1292Hisfs*105). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 197 amino acids of the IQSEC2 protein. |