ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.967G>C (p.Glu323Gln) (rs1057522287)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000434123 SCV000526984 uncertain significance not provided 2019-01-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DSP gene. The E323Q variant has not been published as pathogenic or been reported as benign to our knowledge. The E323Q variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The E323Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Moreover, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this variant has not been observed in a significant number of affected individuals, and there are no segregation or functional studies to further clarify its role in disease.
Invitae RCV000542223 SCV000641363 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with glutamine at codon 323 of the DSP protein (p.Glu323Gln). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and glutamine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a 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 C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

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