ClinVar Miner

Submissions for variant NM_004006.2(DMD):c.2827C>T (p.Arg943Cys) (rs199986217)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000080527 SCV000112429 benign not specified 2016-05-31 criteria provided, single submitter clinical testing
GeneDx RCV000845504 SCV000520969 benign not provided 2019-07-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 25474345, 25231023)
Invitae RCV000990698 SCV000625881 benign Duchenne muscular dystrophy 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000618497 SCV000736119 benign Cardiovascular phenotype 2017-12-27 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845504 SCV000987606 likely benign not provided criteria provided, single submitter clinical testing
Mendelics RCV000990698 SCV001141724 likely benign Duchenne muscular dystrophy 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001167433 SCV001329933 uncertain significance Dilated cardiomyopathy 3B 2017-05-01 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000080527 SCV001364026 benign not specified 2019-02-15 criteria provided, single submitter clinical testing Variant summary: DMD c.2827C>T (p.Arg943Cys) results in a non-conservative amino acid change located in the Spectrin/alpha-actinin repeat of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 199644 control chromosomes, including 14 hemizygotes (gnomAD). The high occurrence in hemizygous control individuals suggests this variant is benign. DMD gene is found to be tolerant to missense changes (Z = -4.82, ExAC) providing further evidence in support of a benign role for the variant. c.2827C>T has been reported in the literature in individuals affected with Stargardt macular dystrophy and dilated cardiomyopathy (Haas_2015, Zaneveld_2015). These reports do not provide unequivocal conclusions about association of the variant with Dystrophiopathies. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign (3x) and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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