ClinVar Miner

Submissions for variant NM_001376.5(DYNC1H1):c.7192C>T (p.Arg2398Cys) (rs141525226)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725688 SCV000338612 uncertain significance not provided 2018-08-10 criteria provided, single submitter clinical testing
GeneDx RCV000374519 SCV000589894 uncertain significance not specified 2017-06-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DYNC1H1 gene. The R2398C variant was identified in a patient with optic atrophy, spastic paraplegia, and axonal neuropathy (Strickland et al., 2015). However, no family members were available for segregation analysis and this variant is listed in dbSNP (rs141525226) and the NHLBI EVS database (albeit at a very low frequency). Therefore, the authors suggest it likely represents a rare polymorphism (Strickland et al., 2015). The R2398C variant is observed in 6/6146 (0.1%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R2398C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory,University of Chicago RCV000374519 SCV000594421 likely benign not specified 2016-08-30 criteria provided, single submitter clinical testing
Invitae RCV001085654 SCV001004721 likely benign Charcot-Marie-Tooth disease, axonal, type 2O 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001085654 SCV001266313 likely benign Charcot-Marie-Tooth disease, axonal, type 2O 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV001114649 SCV001272551 benign Autosomal dominant cerebellar ataxia 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 was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

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