ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.58C>T (p.His20Tyr) (rs201715603)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196976 SCV000251732 benign not specified 2015-08-31 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000556563 SCV000347962 uncertain significance Charcot-Marie-Tooth disease, type 2 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000342413 SCV000347963 uncertain significance Hereditary motor and sensory neuropathy 2016-06-14 criteria provided, single submitter clinical testing
Inherited Neuropathy Consortium RCV000789062 SCV000928411 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only
Invitae RCV000556563 SCV000657729 uncertain significance Charcot-Marie-Tooth disease, type 2 2018-11-21 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 20 of the MFN2 protein (p.His20Tyr). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs201715603, ExAC 0.01%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Charcot-Marie-Tooth disease (PMID: 24957169). ClinVar contains an entry for this variant (Variation ID: 214656). 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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