Submissions for variant NM_014874.4(MFN2):c.2258dup (p.Gln754fs) (rs773371488)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Mendelics	RCV000986248	SCV001135184	uncertain significance	Charcot-Marie-Tooth disease, type 2A2A	2019-05-28	criteria provided, single submitter	clinical testing
Invitae	RCV001232650	SCV001405215	uncertain significance	Charcot-Marie-Tooth disease, type 2	2019-08-14	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the MFN2 gene (p.Gln754Alafs*9). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 4 amino acids of the MFN2 protein and extend the protein by an additional 4 amino acids. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in the heterozygous state in an individual affected with Charcot-Marie-Tooth disease (PMID: 16762064). This variant has also been observed in combination with another MFN2 variant in an individual with Charcot-Marie-Tooth disease; however, this variant did not segregate with disease in affected family members (PMID: 28215760). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Istituto Neurologico Mediterraneo,Istituto di Ricovero e Cura a Carattere Scientifico	RCV000986248	SCV001424047	pathogenic	Charcot-Marie-Tooth disease, type 2A2A	2020-01-26	criteria provided, single submitter	clinical testing
Inherited Neuropathy Consortium	RCV000789613	SCV000928978	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only