Submissions for variant NM_012062.5(DNM1L):c.1834A>T (p.Ile612Phe)

gnomAD frequency: 0.00073  dbSNP: rs138133550

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000195517	SCV000251344	likely benign	not specified	2017-06-05	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.
Mendelics	RCV000988809	SCV001138674	likely benign	Encephalopathy, lethal, due to defective mitochondrial peroxisomal fission 1	2019-05-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001857728	SCV002146154	uncertain significance	not provided	2025-01-27	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 612 of the DNM1L protein (p.Ile612Phe). This variant is present in population databases (rs138133550, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DNM1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 214305). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Ambry Genetics	RCV002517208	SCV003685664	likely benign	Inborn genetic diseases	2021-09-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV001857728	SCV004042543	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	DNM1L: BP4