Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000286162 | SCV000330886 | pathogenic | not provided | 2023-03-24 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect; p.(G550R) abolished GABA transport activity (Mattison et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27824329, 25363768, 28714951, 34011629, 31981491, 31785789, 31332282, 28191890, 30132828) |
Mendelics | RCV003444225 | SCV001136320 | likely pathogenic | Myoclonic-astatic epilepsy | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Genomic Medicine Lab, |
RCV001007935 | SCV001167646 | likely pathogenic | Global developmental delay | 2018-11-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003595908 | SCV001560690 | uncertain significance | Myoclonic-atonic epilepsy | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 550 of the SLC6A1 protein (p.Gly550Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of SLC6A1-related conditions (PMID: 25363768, 27824329, 30132828, 31332282, 31981491; Invitae). ClinVar contains an entry for this variant (Variation ID: 280932). 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 SLC6A1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC6A1 function (PMID: 30132828, 34028503, 36674476). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
Institute of Human Genetics, |
RCV003444225 | SCV004027812 | likely pathogenic | Myoclonic-astatic epilepsy | 2023-06-27 | criteria provided, single submitter | clinical testing | Criteria applied: PS1,PS4_MOD,PM2_SUP,PM5_SUP,PP3 |