Submissions for variant NM_004415.4(DSP):c.968A>G (p.Glu323Gly)

dbSNP: rs1064795408

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000486582	SCV000571177	uncertain significance	not provided	2016-07-29	criteria provided, single submitter	clinical testing	A novel variant of uncertain significance has been identified in the DSP gene. The E323G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The E323G variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The E323G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties, and this substitution occurs at a position that is conserved across species. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, there are no functional studies or segregation data available to clarify the role of this variant in disease.
Invitae	RCV002525884	SCV003314582	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2022-09-13	criteria provided, single submitter	clinical testing	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. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 421859). This variant has not been reported in the literature in individuals affected with DSP-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 323 of the DSP protein (p.Glu323Gly).