Submissions for variant NM_014874.4(MFN2):c.119A>G (p.Asn40Ser)

gnomAD frequency: 0.00003  dbSNP: rs1354203259

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000729317	SCV000856967	uncertain significance	not provided	2017-09-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000729317	SCV001247283	uncertain significance	not provided	2019-10-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001862171	SCV002170675	uncertain significance	Charcot-Marie-Tooth disease type 2	2021-09-25	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with MFN2-related conditions. This sequence change replaces asparagine with serine at codon 40 of the MFN2 protein (p.Asn40Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). ClinVar contains an entry for this variant (Variation ID: 594103). 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"). 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.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000729317	SCV001957373	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000729317	SCV001970118	likely benign	not provided		no assertion criteria provided	clinical testing