ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8210T>C (p.Val2737Ala) (rs794728155)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181390 SCV000233692 uncertain significance not provided 2011-12-22 criteria provided, single submitter clinical testing The Val2737Ala variant in the DSP gene has not been reported previously as a disease-causing mutation, nor as a benign polymorphism, to our knowledge. Although Val2737Ala results in a conservative substitution of one non-polar amino acid for another, the Val2737 residue is conserved across species. The NHLBI ESP Exome Variant Server reports Val2737Ala in 1/3,737 alleles from individuals of African American ancestry. However, no data from ethnically-matched controls are available to assess for a population-specific benign variant. In addition, few disease-causing missense mutations have been reported in this region of the DSP gene, indicating this region of the protein may tolerate change (Van der Zwaag PA et al., 2009). In summary, with the clinical and molecular information available at this time, we cannot determine whether the Val2737Ala variant is a disease-causing mutation or a rare benign variant. The variant is found in ARVC panel(s).
Invitae RCV000791642 SCV000930900 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-08-02 criteria provided, single submitter clinical testing This sequence change replaces valine with alanine at codon 2737 of the DSP protein (p.Val2737Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 199941). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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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