Submissions for variant NM_004082.5(DCTN1):c.100G>C (p.Glu34Gln)

gnomAD frequency: 0.00008  dbSNP: rs151052060

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000997178	SCV001152369	uncertain significance	not provided	2019-04-01	criteria provided, single submitter	clinical testing
Invitae	RCV001036952	SCV001200342	uncertain significance	Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B	2024-01-16	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 34 of the DCTN1 protein (p.Glu34Gln). This variant is present in population databases (rs151052060, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of DCTN1-related conditions (PMID: 23143281, 35047667). ClinVar contains an entry for this variant (Variation ID: 808781). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DCTN1 protein function with a negative predictive value of 80%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on DCTN1 function (PMID: 23143281). 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.
GeneDx	RCV000997178	SCV002004763	uncertain significance	not provided	2020-03-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Published functional studies suggest this variant results in subtle changes in cellular localization, but the biological relevance of this finding is unknown (Stockmann et al., 2013); Identified in a patient with motor neuron disease in published literature, however, this variant was also observed in a healthy control (Stockmann et al., 2013); This variant is associated with the following publications: (PMID: 23143281)
Ambry Genetics	RCV002434383	SCV002746039	uncertain significance	Inborn genetic diseases	2019-10-25	criteria provided, single submitter	clinical testing	The p.E34Q variant (also known as c.100G>C), located in coding exon 2 of the DCTN1 gene, results from a G to C substitution at nucleotide position 100. The glutamic acid at codon 34 is replaced by glutamine, an amino acid with highly similar properties. Functional studies have shown that the p.E34Q variant produces abnormal cellular localization (Stockmann M et al. J Neural Transm (Vienna), 2013 May;120:785-98). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV001036952	SCV002784992	uncertain significance	Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B	2021-11-04	criteria provided, single submitter	clinical testing
Inherited Neuropathy Consortium Ii, University Of Miami	RCV003447313	SCV004174466	uncertain significance	Perry syndrome	2016-01-06	no assertion criteria provided	literature only