ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.1085C>G (p.Thr362Arg) (rs387906991)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458626 SCV000547921 pathogenic Charcot-Marie-Tooth disease, type 2 2020-08-14 criteria provided, single submitter clinical testing This sequence change replaces threonine with arginine at codon 362 of the MFN2 protein (p.Thr362Arg). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in multiple individuals affected with autosomal dominant hereditary sensory and/or motor neuropathy and has been observed to segregate with disease in a family (PMID: 26392352, 26930221, Invitae). ClinVar contains an entry for this variant (Variation ID: 408317). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). This variant disrupts the p.Thr362 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been observed in individuals with MFN2-related conditions (PMID: 18458227, 26114802, 21715711, 16835246), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc RCV000991837 SCV001143625 uncertain significance not provided 2019-08-13 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre RCV001174304 SCV001337436 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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