ClinVar Miner

Submissions for variant NM_004082.4(DCTN1):c.2353C>T (p.Arg785Trp) (rs121909344)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000644476 SCV000766174 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Distal hereditary motor neuronopathy type 7B 2019-12-04 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 785 of the DCTN1 protein (p.Arg785Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs121909344, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in 2 families affected with amyotrophic lateral sclerosis (ALS), but was found in both affected and unaffected family members (PMID: 15326253, 19506225). ClinVar contains an entry for this variant (Variation ID: 8404). Experimental studies have shown that this missense change does not affect cellular morphology or microtubule binding (PMID: 23143281, 18812314). 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.
Fulgent Genetics,Fulgent Genetics RCV000644476 SCV000897052 uncertain significance Amyotrophic lateral sclerosis type 1; Perry syndrome; Distal hereditary motor neuronopathy type 7B 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000986781 SCV001135904 uncertain significance Amyotrophic lateral sclerosis type 1 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001140673 SCV001300954 uncertain significance Distal hereditary motor neuronopathy type 7B 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001140674 SCV001300955 uncertain significance Perry syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000008912 SCV000029122 risk factor Amyotrophic lateral sclerosis, susceptibility to 2004-08-24 no assertion criteria provided literature only
Dept. of Medical Genetics, Telemark Hospital Trust RCV000144867 SCV000172138 uncertain significance Charcot-Marie-Tooth disease 2013-11-01 no assertion criteria provided research

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