Submissions for variant NM_004082.5(DCTN1):c.73C>T (p.Arg25Trp)

gnomAD frequency: 0.00003  dbSNP: rs756611519

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001995802	SCV002277040	uncertain significance	Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B	2023-11-21	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 25 of the DCTN1 protein (p.Arg25Trp). This variant is present in population databases (rs756611519, 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: 1482795). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Department of Neurology, Xijing Hospital, Fourth Military Medical University	RCV002295358	SCV002553226	likely pathogenic	Perry syndrome	2022-03-01	criteria provided, single submitter	clinical testing