Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV000001847 | SCV001164331 | likely pathogenic | Early myoclonic encephalopathy | 2018-12-03 | criteria provided, single submitter | research | The homozygous p.Pro206Leu variant in SLC25A22 was identified by our study in one individual with Epileptic Encephalopathy. This variant has been identified in the literature in four affected siblings. Functional assays showed mutant functionality to be 20% of wild-type. (Molinari et al. 2005, PMID: 15592994). This variant has been identified in <0.01% (2/15258) of African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121918334). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. |
Invitae | RCV001851565 | SCV002244727 | pathogenic | Early infantile epileptic encephalopathy with suppression bursts | 2022-12-31 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects SLC25A22 function (PMID: 25033742). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SLC25A22 protein function. ClinVar contains an entry for this variant (Variation ID: 1775). This missense change has been observed in individuals with SLC25A22-related conditions (PMID: 15592994, 25033742). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121918334, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 206 of the SLC25A22 protein (p.Pro206Leu). |
OMIM | RCV002508754 | SCV000022003 | pathogenic | Developmental and epileptic encephalopathy, 3 | 2005-02-01 | no assertion criteria provided | literature only |