ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.25270C>T (p.Arg8424Trp) (rs373551215)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521206 SCV000619360 uncertain significance not provided 2017-07-20 criteria provided, single submitter clinical testing The R8424W variant in the NEB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R8424W variant is observed in 10/12108 (0.08%) alleles from individuals of South Asian background, in the ExAC dataset (Lek et al., 2016). The R8424W 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. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret R8424W as a variant of uncertain significance.
Illumina Clinical Services Laboratory,Illumina RCV000289896 SCV000416809 uncertain significance Nemaline Myopathy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000536760 SCV000640753 uncertain significance Nemaline myopathy 2 2017-06-20 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 8424 of the NEB protein (p.Arg8424Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs373551215, ExAC 0.08%). This variant has not been reported in the literature in individuals with an NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 331403). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious";  Align-GVGD: "Class C0"). In summary, this variant has uncertain impact on NEB function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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