ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.3145C>T (p.Arg1049Trp)

gnomAD frequency: 0.00002  dbSNP: rs573012389
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001813030 SCV001473273 uncertain significance not provided 2019-09-17 criteria provided, single submitter clinical testing The DCTN1 c.3145C>T; p.Arg1049Trp variant (rs573012389), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 1049 is highly conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg1049Trp variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001871686 SCV002166433 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2023-11-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1049 of the DCTN1 protein (p.Arg1049Trp). This variant is present in population databases (rs573012389, gnomAD 0.01%). This missense change has been observed in individuals with amyotrophic lateral sclerosis (PMID: 28792508; Invitae). ClinVar contains an entry for this variant (Variation ID: 994029). 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 expected to disrupt DCTN1 protein function with a positive predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen RCV001813030 SCV004155062 uncertain significance not provided 2023-03-01 criteria provided, single submitter clinical testing DCTN1: PM2

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