ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.1598T>C (p.Leu533Pro)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002848752 SCV003612933 uncertain significance Inborn genetic diseases 2022-04-07 criteria provided, single submitter clinical testing The c.1598T>C (p.L533P) alteration is located in exon 15 (coding exon 13) of the MFN2 gene. This alteration results from a T to C substitution at nucleotide position 1598, causing the leucine (L) at amino acid position 533 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003581885 SCV004282451 uncertain significance Charcot-Marie-Tooth disease type 2 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 533 of the MFN2 protein (p.Leu533Pro). This variant is not present in population databases (gnomAD no frequency). 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: 2282373). 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 with a positive predictive value of 95%. 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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