ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.1759C>T (p.Pro587Ser)

gnomAD frequency: 0.00003  dbSNP: rs771675874
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, London Health Sciences Centre RCV001174299 SCV001337431 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001858530 SCV002237577 uncertain significance Charcot-Marie-Tooth disease type 2 2025-01-01 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 587 of the MFN2 protein (p.Pro587Ser). This variant is present in population databases (rs771675874, gnomAD 0.004%). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 32376792, 37273706). ClinVar contains an entry for this variant (Variation ID: 694952). Invitae Evidence 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 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 RCV002399858 SCV002711707 uncertain significance Inborn genetic diseases 2023-08-01 criteria provided, single submitter clinical testing The c.1759C>T (p.P587S) alteration is located in exon 16 (coding exon 14) of the MFN2 gene. This alteration results from a C to T substitution at nucleotide position 1759, causing the proline (P) at amino acid position 587 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Athena Diagnostics RCV002473156 SCV002771030 uncertain significance not provided 2023-03-08 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function.
Breakthrough Genomics, Breakthrough Genomics RCV002473156 SCV005186465 uncertain significance not provided criteria provided, single submitter not provided
Genesis Genome Database RCV000857110 SCV000999685 uncertain significance Charcot-Marie-Tooth disease type 4 2019-08-14 no assertion criteria provided research

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