ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8309A>G (p.Tyr2770Cys)

gnomAD frequency: 0.00001  dbSNP: rs371020228
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute RCV000622872 SCV000740332 uncertain significance Primary familial dilated cardiomyopathy 2017-01-29 criteria provided, single submitter clinical testing
Invitae RCV000796620 SCV000936140 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-10-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001185277 SCV001351452 uncertain significance Cardiomyopathy 2023-03-23 criteria provided, single submitter clinical testing This missense variant replaces tyrosine with cysteine at codon 2770 of the DSP protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 27532257). This variant has been identified in 5/251412 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV002259357 SCV002538711 uncertain significance not provided 2022-05-26 criteria provided, single submitter clinical testing Observed in an individual with ARVC in the published literature (Walsh et al., 2017); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27532257, 31402444)
Ambry Genetics RCV002431833 SCV002681950 uncertain significance Cardiovascular phenotype 2018-06-25 criteria provided, single submitter clinical testing The p.Y2770C variant (also known as c.8309A>G), located in coding exon 24 of the DSP gene, results from an A to G substitution at nucleotide position 8309. The tyrosine at codon 2770 is replaced by cysteine, an amino acid with highly dissimilar properties. This variant has been reported in individual from an arrhythmogenic right ventricular cardiomyopathy (ARVC) genetic testing cohort; however, clinical details were not provided (Walsh R et al. Genet. Med., 2017 02;19:192-203). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.