ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7738G>T (p.Asp2580Tyr) (rs371129517)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000253165 SCV000320311 uncertain significance Cardiovascular phenotype 2017-04-29 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
GeneDx RCV000483520 SCV000571754 uncertain significance not provided 2016-09-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DSP gene. The D2580Y variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant was not observed at a significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D2580Y 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. However, this substitution occurs at a position that is not conserved across species. Furthermore, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000825918 SCV000967403 uncertain significance not specified 2018-02-07 criteria provided, single submitter clinical testing The p.Asp2580Tyr variant in DSP has not been previously reported in individuals with cardiomyopathy, but has been identified in 4/24036 African chromosomes by t he Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs371129517). This variant has been reported in ClinVar (Variation ID: 264394). Please note that for diseases with clinical variability, reduced penetrance, or recessive inheritance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and conservation analysi s do not provide strong support for or against an impact to the protein. In summ ary, the clinical significance of the p.Asp2580Tyr variant is uncertain. ACMG/AM P Criteria applied: None (Richards 2015).

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