ClinVar Miner

Submissions for variant NM_033409.4(SLC52A3):c.796C>T (p.Arg266Trp) (rs370499474)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483942 SCV000567641 uncertain significance not provided 2018-07-02 criteria provided, single submitter clinical testing The R266W variant in the SLC52A3 gene has been reported previously in association with autosomal recessive Brown-Vialetto-Van Laere syndrome 1 (Ciccolella et al., 2012). has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is observed in 5/126660 (0.0039%) alleles from individuals of non-Finnish European background in large population cohorts, with no homozygotes identified (Lek et al., 2016). The R266W 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. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function.We interpret R266W as a variant of uncertain significance.
Invitae RCV000191965 SCV000942847 uncertain significance Brown-Vialetto-Van Laere syndrome 1 2018-07-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 266 of the SLC52A3 protein (p.Arg266Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs370499474, ExAC 0.003%). This variant has been observed in combination with another SLC52A3 variant in an individual affected with Brown-Vialetto-Van Laere syndrome 1 (PMID: 22824638). ClinVar contains an entry for this variant (Variation ID: 210020). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
GeneReviews RCV000191965 SCV000246220 pathogenic Brown-Vialetto-Van Laere syndrome 1 2015-03-17 no assertion criteria provided literature only

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