ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.1555C>T (p.Arg519Cys)

dbSNP: rs369140232
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000626139 SCV000746770 uncertain significance Charcot-Marie-Tooth disease type 2A2 2023-10-07 criteria provided, single submitter clinical testing
Invitae RCV002529779 SCV003020627 uncertain significance Charcot-Marie-Tooth disease type 2 2023-11-07 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 519 of the MFN2 protein (p.Arg519Cys). This variant is present in population databases (no rsID available, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MFN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 522942). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MFN2 protein function. 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.
Ambry Genetics RCV003352943 SCV004077571 uncertain significance Inborn genetic diseases 2023-07-17 criteria provided, single submitter clinical testing The c.1555C>T (p.R519C) alteration is located in exon 15 (coding exon 13) of the MFN2 gene. This alteration results from a C to T substitution at nucleotide position 1555, causing the arginine (R) at amino acid position 519 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Coban-Akdemir Lab, University of Texas Health Science Center RCV003483693 SCV004231752 uncertain significance Multiple symmetric lipomatosis; Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b; no assertion criteria provided research

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