Submissions for variant NM_014874.3(MFN2):c.1452G>A (p.Thr484=) (rs150043585)

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000198508	SCV000226139	likely benign	not specified	2017-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000198508	SCV000251701	benign	not specified	2014-11-14	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000205476	SCV000262335	likely benign	Charcot-Marie-Tooth disease, type 2	2019-12-31	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000205476	SCV000347989	benign	Charcot-Marie-Tooth disease, type 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina	RCV000391814	SCV000347990	benign	Hereditary motor and sensory neuropathy with optic atrophy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Athena Diagnostics Inc	RCV000198508	SCV000614084	benign	not specified	2017-02-13	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001172694	SCV001335760	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen	RCV001200326	SCV001371250	likely benign	not provided	2020-04-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001200326	SCV001433778	likely benign	not provided	2017-06-07	criteria provided, single submitter	clinical testing	The c.1452G>A; p.Thr484Thr variant (rs150043585, ClinVar ID 194409) does not alter the amino acid sequence of the MFN2 protein and computational splice site prediction algorithms do not predict a change in the nearest splice site; however, computational analysis predicts the possible creation of a cryptic splice acceptor site in exon 14, though no published evidence exists to support or refute this prediction. This variant has not been reported in association with mitochondrial disease in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with a non-Finnish European population frequency of 0.1% (identified on 153 out of 125,638 chromosomes). Based on the available information, the c.1452G>A variant is likely to be benign.