ClinVar Miner

Submissions for variant NM_014874.3(MFN2):c.842G>C (p.Cys281Ser) (rs147136530)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000767173 SCV000251713 uncertain significance not provided 2019-01-07 criteria provided, single submitter clinical testing A variant of unknown significance has been identified in the MFN2 gene. It has been reported in families with axonal hereditary motor and sensory neuropathy; however, the authors concluded that C281S is either a benign variant or a pathogenic variant associated with autosomal recessive inheritance as it was identified in healthy relatives with normal electrophysiological examination (Brozkova et al., 2013). The C281S variant is observed in 24/9838 (0.2%) alleles from individuals of Ashkenazi Jewish background, (Lek et al., 2016). However, the C281S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Additionally, missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with Charcot-Marie-Tooth disease type 2A (Stenson et al., 2009). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Athena Diagnostics Inc RCV000199052 SCV000614095 likely benign not specified 2016-12-19 criteria provided, single submitter clinical testing
Invitae RCV001087915 SCV000775857 likely benign Charcot-Marie-Tooth disease, type 2 2020-11-17 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001087915 SCV001256163 likely benign Charcot-Marie-Tooth disease, type 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001099689 SCV001256164 uncertain significance Hereditary motor and sensory neuropathy with optic atrophy 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Molecular Genetics Laboratory,London Health Sciences Centre RCV001174298 SCV001337430 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Baylor Genetics RCV001331980 SCV001524158 uncertain significance Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2A2B 2020-01-23 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic RCV000767173 SCV001715253 uncertain significance not provided 2019-07-15 criteria provided, single submitter clinical testing

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