ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6479G>A (p.Arg2160Gln) (rs146642551)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181343 SCV000233640 uncertain significance not provided 2016-04-06 criteria provided, single submitter clinical testing The R2160Q variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R2160Q 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. The R1260Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, this substitution occurs at a position that is conserved in mammals. Nevertheless, in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Illumina Clinical Services Laboratory,Illumina RCV000291872 SCV000465170 uncertain significance Ectodermal dysplasia skin fragility syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000344461 SCV000465171 uncertain significance Epidermolysis bullosa, lethal acantholytic 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000406693 SCV000465172 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000295633 SCV000465173 uncertain significance Skin fragility woolly hair syndrome 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000800064 SCV000939762 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-11-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 2160 of the DSP protein (p.Arg2160Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs146642551, ExAC 0.02%). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 199904). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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