ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.493C>T (p.His165Tyr) (rs119103262)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506106 SCV000604222 pathogenic not specified 2017-01-26 criteria provided, single submitter clinical testing
Invitae RCV000802072 SCV000941885 pathogenic Charcot-Marie-Tooth disease, type 2 2018-09-07 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 165 of the MFN2 protein (p.His165Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with dominant Charcot-Marie-Tooth disease in several families (PMID: 16714318, 24126688) and has also been observed in an individual affected with peripheral neuropathy (PMID:27549087). ClinVar contains an entry for this variant (Variation ID: 439897). 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: "Deleterious"; 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 observed in affected individuals (PMID: 16835246, 16714318, 24819634, 17309650), 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.
Inherited Neuropathy Consortium RCV000789411 SCV000928766 uncertain significance Charcot-Marie-Tooth disease no assertion criteria provided literature only

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