ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.7465G>A (p.Asp2489Asn) (rs760552749)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000641820 SCV000763470 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-12-21 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 2489 of the DSP protein (p.Asp2489Asn). The aspartic acid residue is highly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs760552749, ExAC 0.001%). This variant has not been reported in the literature in individuals with DSP-related disease. 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: "Probably 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756046 SCV000883756 uncertain significance not provided 2018-05-06 criteria provided, single submitter clinical testing The p.Asp2489Asn variant (rs760552749) has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.001 percent (identified on 4 out of 277,224 chromosomes). The aspartic acid at position 2489 is highly conserved up to C. elegans considering 12 species (Alamut v2.11) and computational analyses of the p.Asp2489Asn variant on protein structure and function indicate a deleterious effect (SIFT: damaging, PolyPhen-2: probably damaging). Altogether, there is not enough evidence to classify the p.Asp2489Asn variant with certainty.

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