ClinVar Miner

Submissions for variant NM_004082.5(DCTN1):c.175G>A (p.Gly59Ser)

dbSNP: rs121909342
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000644484 SCV000766182 pathogenic Amyotrophic lateral sclerosis type 1; Perry syndrome; Neuronopathy, distal hereditary motor, type 7B 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 59 of the DCTN1 protein (p.Gly59Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change reduces the ability of the dynactin protein to properly bind microtubules and leads to protein aggregation and loss of motor neurons (PMID: 12627231, 19279216, 16505168, 23143281). Additionally, several mouse models have recapitulated the disease phenotype observed in individuals carrying this variant. (PMID: 18364389, 18094236). This variant has been reported to segregate with hereditary motor neuropathy, type 7B in a single family and has also been reported in additional, unrelated affected individuals (PMID: 12627231, 27573046 ). ClinVar contains an entry for this variant (Variation ID: 8401).
OMIM RCV000008909 SCV000029119 pathogenic Neuronopathy, distal hereditary motor, type 7B 2009-03-31 no assertion criteria provided literature only
Inherited Neuropathy Consortium RCV000789086 SCV000928435 uncertain significance Hereditary motor neuron disease no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV003447080 SCV004174443 uncertain significance Perry syndrome 2016-01-06 no assertion criteria provided literature only

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