Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001224070 | SCV001396247 | uncertain significance | GLUT1 deficiency syndrome 1, autosomal recessive | 2021-05-26 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 SLC2A1 protein function. This variant has been observed in two siblings affected with epilepsy (PMID: 23280796, 28717674). ClinVar contains an entry for this variant (Variation ID: 96709). This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 411 of the SLC2A1 protein (p.Asn411Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. Experimental studies have shown that this variant affects SLC2A1 protein function (PMID: 23280796). |
Gene |
RCV001588909 | SCV001816654 | pathogenic | not provided | 2022-02-24 | criteria provided, single submitter | clinical testing | Published functional studies with Xenopus oocytes demonstrate mild reduction in glucose transport (Arsov et al., 2012; Zaman et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28717674, 30588498, 23280796, Guzmn-Jimnez2019[Review], 33806661) |
OMIM | RCV000082869 | SCV000114920 | risk factor | Epilepsy, idiopathic generalized, susceptibility to, 12 | 2012-11-01 | no assertion criteria provided | literature only |