ClinVar Miner

Submissions for variant NM_006158.4(NEFL):c.761T>C (p.Leu254Pro) (rs1554497578)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000640657 SCV000762252 uncertain significance Charcot-Marie-Tooth disease type 2E 2017-12-15 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 254 of the NEFL protein (p.Leu254Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NEFL-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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