ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8191T>C (p.Tyr2731His) (rs201397978)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172545 SCV000055171 likely benign not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000150582 SCV000197851 uncertain significance not specified 2014-03-19 criteria provided, single submitter clinical testing The Tyr2731His variant in DSP has been reported in 1 individual with HCM (Lopes 2013) and has been identified by our laboratory in 4 Indian individuals with HCM (including this individual). It has also been identified in 1/854 control chrom osomes (Kapplinger 2011) and in 1/4406 African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs201397978) . Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. At this time, additional infor mation is needed to fully assess the clinical significance of the Tyr2731His var iant.
GeneDx RCV000150582 SCV000233647 benign not specified 2017-06-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Clinical Services Laboratory,Illumina RCV000407212 SCV000465238 likely benign Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000299334 SCV000465239 likely benign Skin fragility woolly hair syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000356762 SCV000465240 likely benign Epidermolysis bullosa, lethal acantholytic 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000259603 SCV000465241 likely benign Ectodermal dysplasia skin fragility syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000172545 SCV000555757 benign not provided 2018-10-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000172545 SCV000698450 benign not provided 2017-07-10 criteria provided, single submitter clinical testing Variant summary: The DSP c.8191T>C (p.Tyr2731His) variant involves the alteration of a conserved nucleotide, resulting in a missense substitution in a plectin repeat domain (InterPro). 3/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in the large control database ExAC and control cohorts from the literature in 341of 122076 control chromosomes (6 homozygotes) from all ethnicities, but was predominantly observed in the South Asian subpopulation at a frequency of 0.020288 (335/16512 chromosomes; 6 homozygotes). This frequency is about 2029 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.00001), strongly suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant has been reported in both controls and arrythmia patients in the literature (Lopes_J Med Genet_2013; Kapplinger_JACC_2011; Ng_Circ_2013), with authors describing the variant as a rare polymorphism and classifying as VUS or likely benign. Multiple clinical diagnostic laboratories/reputable databases have classified this variant as likely benign or benign after 2014. Taken together, this variant is classified as benign.
Color RCV000771201 SCV000903195 benign Cardiomyopathy 2018-10-01 criteria provided, single submitter clinical testing

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