ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.1915C>T (p.Arg639Trp)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002926945 SCV003256938 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2022-11-08 criteria provided, single submitter clinical testing 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. 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. This missense change has been observed in individual(s) with amyotrophic lateral sclerosis (PMID: 26742954). This variant is present in population databases (rs776398707, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 639 of the DCTN1 protein (p.Arg639Trp).
GeneDx RCV003227078 SCV003923598 uncertain significance not provided 2022-11-02 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Previously reported in association with ALS; however detailed family history and phenotypic details were not provided (Nakamura et al., 2016; Liu et al., 2019); This variant is associated with the following publications: (PMID: 26742954, 32293029, 31788332)
Ambry Genetics RCV003269311 SCV003946766 uncertain significance Inborn genetic diseases 2023-04-03 criteria provided, single submitter clinical testing The c.1915C>T (p.R639W) alteration is located in exon 17 (coding exon 17) of the DCTN1 gene. This alteration results from a C to T substitution at nucleotide position 1915, causing the arginine (R) at amino acid position 639 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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