ClinVar Miner

Submissions for variant NM_014874.4(MFN2):c.163A>T (p.Thr55Ser)

gnomAD frequency: 0.00001  dbSNP: rs776423551
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000711271 SCV000620693 uncertain significance not provided 2019-11-19 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV000534867 SCV000657713 uncertain significance Charcot-Marie-Tooth disease type 2 2024-09-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 55 of the MFN2 protein (p.Thr55Ser). This variant is present in population databases (rs776423551, gnomAD 0.002%). 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: 451931). 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) indicates that this missense variant is not expected to disrupt MFN2 protein function with a negative predictive value of 80%. 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.
Athena Diagnostics RCV000711271 SCV000841607 uncertain significance not provided 2024-01-18 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) This variant has been seen where an alternate explanation for disease was also identified, suggesting this variant may not cause disease. Computational tools predict that this variant is not damaging.
Ambry Genetics RCV002525222 SCV003613882 uncertain significance Inborn genetic diseases 2022-02-03 criteria provided, single submitter clinical testing The c.163A>T (p.T55S) alteration is located in exon 3 (coding exon 1) of the MFN2 gene. This alteration results from a A to T substitution at nucleotide position 163, causing the threonine (T) at amino acid position 55 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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