ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.10181T>C (p.Ile3394Thr) (rs376182104)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000267771 SCV000416946 uncertain significance Nemaline Myopathy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000518845 SCV000619797 uncertain significance not provided 2018-02-23 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the NEB gene. The I3394T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I3394T variant is observed in 7/111,520 (0.006%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). The I3394T 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. However, in-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000704366 SCV000833312 uncertain significance Nemaline myopathy 2 2018-03-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 3394 of the NEB protein (p.Ile3394Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs376182104, ExAC 0.009%). This variant has not been reported in the literature in individuals with NEB-related disease. ClinVar contains an entry for this variant (Variation ID: 331481). 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.
Fulgent Genetics,Fulgent Genetics RCV000704366 SCV000895285 uncertain significance Nemaline myopathy 2 2018-10-31 criteria provided, single submitter clinical testing

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