ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.17203G>A (p.Ala5735Thr) (rs202111641)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523201 SCV000619221 uncertain significance not provided 2017-07-25 criteria provided, single submitter clinical testing The A5735T variant in the NEB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A5735T 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 in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A5735T as a variant of uncertain significance.
Invitae RCV000685820 SCV000813319 uncertain significance Nemaline myopathy 2 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 5735 of the NEB protein (p.Ala5735Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs202111641, ExAC 0.005%). This variant has not been reported in the literature in individuals with NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 450617). 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. RCV000685820 SCV001454706 uncertain significance Nemaline myopathy 2 2020-01-24 no assertion criteria provided clinical testing

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