ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.493C>G (p.His165Asp) (rs119103262)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001208639 SCV001380038 pathogenic Charcot-Marie-Tooth disease, type 2 2019-08-29 criteria provided, single submitter clinical testing This sequence change replaces histidine with aspartic acid at codon 165 of the MFN2 protein (p.His165Asp). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with autosomal dominant Charcot-Marie-Tooth disease with pyramidal features in a large family (PMID: 16087932). ClinVar contains an entry for this variant (Variation ID: 2275). 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.His165 amino acid residue in MFN2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16835246, 16714318, 24819634, 17309650, 24126688, 27549087). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002363 SCV000022521 pathogenic Charcot-Marie-Tooth disease, type 2A2A 2005-08-09 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789416 SCV000928771 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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