Submissions for variant NM_004082.5(DCTN1):c.1504C>T (p.Arg502Cys)

dbSNP: rs145958900

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001046553	SCV001210458	uncertain significance	Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B	2023-08-20	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 502 of the DCTN1 protein (p.Arg502Cys). This variant is present in population databases (rs145958900, gnomAD 0.01%). 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: 843850). 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. 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.
Athena Diagnostics	RCV001288144	SCV001475060	uncertain significance	not provided	2020-03-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001288144	SCV002006089	uncertain significance	not provided	2019-07-09	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002393231	SCV002702394	uncertain significance	Inborn genetic diseases	2021-11-17	criteria provided, single submitter	clinical testing	The p.R502C variant (also known as c.1504C>T), located in coding exon 14 of the DCTN1 gene, results from a C to T substitution at nucleotide position 1504. The arginine at codon 502 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV001046553	SCV002781228	uncertain significance	Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B	2021-11-12	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003898052	SCV004710719	uncertain significance	DCTN1-related disorder	2023-12-31	criteria provided, single submitter	clinical testing	The DCTN1 c.1504C>T variant is predicted to result in the amino acid substitution p.Arg502Cys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.018% of alleles in individuals of European (Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
GenomeConnect - Invitae Patient Insights Network	RCV001046553	SCV001749385	not provided	Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 04-22-2019 by Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.