Submissions for variant NM_004082.5(DCTN1):c.1595G>A (p.Arg532Gln)

gnomAD frequency: 0.00003  dbSNP: rs759306485

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000703147	SCV000832033	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 arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 532 of the DCTN1 protein (p.Arg532Gln). This variant is present in population databases (rs759306485, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DCTN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 579780). 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%. 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	RCV001091892	SCV001248162	uncertain significance	not provided	2019-07-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001091892	SCV004564574	uncertain significance	not provided	2023-11-02	criteria provided, single submitter	clinical testing	The DCTN1 c.1595G>A; p.Arg532Gln variant (rs759306485), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 579780). This variant is found in the general population with an overall allele frequency of 0.001% (3/282,860 alleles) in the Genome Aggregation Database. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.466). Due to limited information, the clinical significance of this variant is uncertain at this time.
Ambry Genetics	RCV004026620	SCV004854776	uncertain significance	Inborn genetic diseases	2023-10-14	criteria provided, single submitter	clinical testing	The c.1595G>A (p.R532Q) alteration is located in exon 15 (coding exon 15) of the DCTN1 gene. This alteration results from a G to A substitution at nucleotide position 1595, causing the arginine (R) at amino acid position 532 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001091892	SCV001951319	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001091892	SCV001974173	uncertain significance	not provided		no assertion criteria provided	clinical testing