ClinVar Miner

Submissions for variant NM_006516.3(SLC2A1):c.277C>T (p.Arg93Trp) (rs267607061)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442654 SCV000520908 pathogenic not provided 2018-08-24 criteria provided, single submitter clinical testing The R93W variant in the SLC2A1 gene has been reported previously in multiple unrelated individuals with glucose transporter type 1 deficiency syndrome (Glut1-DS) (Rotstein et al., 2009; Leen et al., 2010). The R93W variant is not observed in large population cohorts (Lek et al., 2016). The R93W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Functional studies suggest that the R93W variant results in reduced glucose uptake (Pascual et al., 2008). We interpret R93W as a pathogenic variant.
Invitae RCV000648074 SCV000769884 pathogenic GLUT1 deficiency syndrome 1, autosomal recessive 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 93 of the SLC2A1 protein (p.Arg93Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals with low cerebral spinal fluid blood glucose concentrations, findings that are highly specific for GLUT1 deficiency syndrome (PMID: 23106342, 18403583). This includes 1 individual who was found to be de novo for this variant (PMID: 19996082). This variant was also found to segregate with disease in an affected family (PMID: 23448551, 20129935). ClinVar contains an entry for this variant (Variation ID: 16117). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000030922 SCV000037769 pathogenic GLUT1 deficiency syndrome 2 2009-12-08 no assertion criteria provided literature only

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