ClinVar Miner

Submissions for variant NM_001005360.2(DNM2):c.83A>T (p.His28Leu) (rs774962668)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000641100 SCV000762722 uncertain significance Charcot-Marie-Tooth disease, dominant intermediate B 2017-09-13 criteria provided, single submitter clinical testing This sequence change replaces histidine with leucine at codon 28 of the DNM2 protein (p.His28Leu). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and leucine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with DNM2-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 tolerated, 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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