Submissions for variant NM_004415.4(DSP):c.2708A>G (p.Tyr903Cys)

dbSNP: rs777613109

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181379	SCV000233680	uncertain significance	not provided	2014-10-14	criteria provided, single submitter	clinical testing	p.Tyr903Cys (TAT>TGT): c.2708 A>G in exon 19 of the DSP gene (NM_004415.2). The Y903C variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The Y903C variant was not observed in approximately 6,500 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 Y903C 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. Additionally, this substitution occurs at a position that is conserved in most mammals. However, in silico analysis predicts this variant likely does not alter the protein structure/function. Furthermore, missense mutations in nearby residues have not been reported, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in ARRHYTHMIA panel(s).