ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5363A>G (p.Gln1788Arg) (rs139673146)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000168651 SCV000233625 uncertain significance not specified 2016-06-30 criteria provided, single submitter clinical testing The Q1788R variant has not been published as a pathogenic variant or as a benign variant to our knowledge. The Q1788R variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. This substitution occurs at a position that is conserved across species. Nevertheless, the Q1788R variant is a semi-conservative amino acid substitution, which may or may not impact secondary protein structure as these residues differ in some properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, no missense variants in nearby residues have been reported in the HGMD in association with cardiomyopathy (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether the Q1788R variant in the DSP gene is pathogenic or benign.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000168651 SCV000271734 uncertain significance not specified 2014-12-31 criteria provided, single submitter clinical testing The p.Gln1788Arg variant in DSP has not been previously reported in individuals with cardiomyopathy but has been identified in 7/65960 of European chromosomes b y the Exome Aggregation Consortium (ExAC,; dbSNP rs139673146). Computational prediction tools and conservation analysis do not pr ovide strong support for or against an impact to the protein. In summary, the cl inical significance of the p.Gln1788Arg variant is uncertain.
Invitae RCV000797985 SCV000937577 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-11-30 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 1788 of the DSP protein (p.Gln1788Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs139673146, ExAC 0.01%). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 188469). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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