ClinVar Miner

Submissions for variant NM_006158.4(NEFL):c.65C>A (p.Pro22His) (rs267607538)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000205038 SCV000259292 uncertain significance Charcot-Marie-Tooth disease type 2E 2015-07-06 criteria provided, single submitter clinical testing This sequence change replaces proline with histidine at codon 22 of the NEFL protein (p.Pro22His). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and histidine. This variant has not been published in the literature and is not present in population databases. While this p.Pro22His missense change has not been observed before, several different missense substitutions at this codon (p.Pro22Thr, p.Pro22Arg, Pro22Ser) are reported to be deleterious (PMID: 12477167, 12481988, 15111691, 16452125, 18758688, 19286384, 20301384, 21168446). This indicates that the proline residue is important for NEFL protein function. 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: "C0"). In summary, this is a rare missense change with uncertain impact on protein function but affecting a possibly important part of the protein. It has been classified as a Variant of Uncertain Significance.

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