ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.1723C>T (p.Arg575Cys)

dbSNP: rs786204244
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000168427 SCV000219124 uncertain significance Charcot-Marie-Tooth disease type 2 2023-08-24 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with MFN2-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MFN2 protein function. ClinVar contains an entry for this variant (Variation ID: 188378). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 575 of the MFN2 protein (p.Arg575Cys).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV005406876 SCV006071281 uncertain significance not specified 2025-03-26 criteria provided, single submitter clinical testing Variant summary: MFN2 c.1723C>T (p.Arg575Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251348 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1723C>T in individuals affected with Charcot-Marie Disease, Axonal, Autosomal Recessive, Type 2a2b and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 188378). Based on the evidence outlined above, the variant was classified as uncertain significance.

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