Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003362736 | SCV004072584 | uncertain significance | Inborn genetic diseases | 2023-07-25 | criteria provided, single submitter | clinical testing | The c.254T>C (p.L85P) alteration is located in exon 3 (coding exon 3) of the SLC1A2 gene. This alteration results from a T to C substitution at nucleotide position 254, causing the leucine (L) at amino acid position 85 to be replaced by a proline (P). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant has been determined to be the result of a de novo mutation in one individual with features consistent with SLC1A2-related developmental and epileptic encephalopathy (Myers, 2016). This amino acid position is highly conserved in available vertebrate species. Functional studies show that the p.L85P alteration decreases transport activity (Stergachis, 2019; Qu, 2022; Kovermann, 2022). The in silico prediction for this alteration is inconclusive. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003556299 | SCV004294759 | pathogenic | not provided | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 85 of the SLC1A2 protein (p.Leu85Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with epileptic encephalopathy (PMID: 27476654, 30937933). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 254266). 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) performed at Invitae indicates that this missense variant is expected to disrupt SLC1A2 protein function. Experimental studies have shown that this missense change affects SLC1A2 function (PMID: 30937933, 34961934). For these reasons, this variant has been classified as Pathogenic. |
| OMIM | RCV000240924 | SCV000299356 | pathogenic | Developmental and epileptic encephalopathy, 41 | 2013-09-12 | no assertion criteria provided | literature only |