ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.9047G>A (p.Arg3016Gln) (rs373587647)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519197 SCV000619983 uncertain significance not provided 2017-08-17 criteria provided, single submitter clinical testing The R3016Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R3016Q variant is observed in 15/8,262 (0.18%) alleles from individuals of East Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. However, most reported pathogenic variants in the NEB gene are truncating/loss-of-function. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Invitae RCV000556075 SCV000640886 uncertain significance Nemaline myopathy 2 2019-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 3016 of the NEB protein (p.Arg3016Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs373587647, ExAC 0.2%). This variant has not been reported in the literature in individuals with NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 451307). 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, 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.
Natera, Inc. RCV000556075 SCV001454971 uncertain significance Nemaline myopathy 2 2019-11-11 no assertion criteria provided clinical testing

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