ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.47G>C (p.Arg16Pro) (rs752387234)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181354 SCV000233654 uncertain significance not provided 2013-08-12 criteria provided, single submitter clinical testing p.Arg16Pro (CGC>CCC): c.47 G>C in exon 1 of the DSP gene (NM_004415.2). The Arg16Pro variant in the DSP gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Arg16Pro results in a non-conservative amino acid substitution of a positively charged Arginine with a non-polar Proline at a position that is conserved across species when present. In silico analysis predicts Arg16Pro is probably damaging to the protein structure/function. Nevertheless, no mutations in nearby residues have been reported in association with ARVC, indicating this region of the protein may be tolerant of change. Data from control individuals were not available to assess whether Arg16Pro may be a common benign variant in the general population. With the clinical and molecular information available at this time, we cannot definitively determine if Arg16Pro is a disease-causing mutation or a rare benign variant. The variant is found in ARVC panel(s).
Invitae RCV000691756 SCV000819546 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-07-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 16 of the DSP protein (p.Arg16Pro). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and proline. 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: 199913). 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: "Deleterious"; PolyPhen-2: "Benign"; 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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