ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.386C>T (p.Thr129Ile)

dbSNP: rs1060501919
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000459621 SCV000547933 uncertain significance Charcot-Marie-Tooth disease type 2 2018-09-06 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Thr129 amino acid residue in MFN2. Other variants that disrupt this residue have been observed in affected individuals (PMID: 26801520, 28215760), which suggests that this may be a clinically significant amino acid residue. 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. This variant has not been reported in the literature in individuals with MFN2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 129 of the MFN2 protein (p.Thr129Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine.

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