ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.12905A>T (p.Asn4302Ile)

gnomAD frequency: 0.00046  dbSNP: rs886038429
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000249817 SCV000307201 likely benign not specified criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000545964 SCV000640539 uncertain significance Nemaline myopathy 2 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine with isoleucine at codon 4302 of the NEB protein (p.Asn4302Ile). The asparagine residue is weakly conserved and there is a large physicochemical difference between asparagine and isoleucine. This variant occurs in a region of NEB (Exons 82-105) consisting of three highly homologous 8-exon repeat units (exons 82-89, exons 90-97, exons 98-105). Sequence variants in this region can be detected, but this assay cannot determine which of the three repeat units is affected, and zygosity is often ambiguous. All variants in this region are reported relative to the exon 82-89 repeat. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a NEB-related disease. 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"; PolyPhen-2: "probably damaging"; Align-GVGD: "Class C0"). In summary, this variant is a novel missense change with uncertain impact on protein function. Missense variants in the NEB gene are typically not pathogenic, and there is no indication that this variant causes disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV001705346 SCV000730868 likely benign not provided 2021-03-23 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25205138)
Natera, Inc. RCV000545964 SCV001460873 uncertain significance Nemaline myopathy 2 2019-11-11 no assertion criteria provided clinical testing

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