Submissions for variant NM_000891.3(KCNJ2):c.211G>A (p.Asp71Asn)

dbSNP: rs199473369

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413768	SCV000491129	likely pathogenic	not provided	2016-04-21	criteria provided, single submitter	clinical testing	A variant that is likely pathogenic was identified in the KCNJ2 gene. The D71N variant has been reported as a de novo variant in a patient with ATS, and it was not identified in 100 control individual (Donaldson et al., 2003). The D71N 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 D71N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Finally, a missense variant in the same residue (D71V) has been reported in the Human Gene Mutation Database in association with ATS (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000058297	SCV000089817	not provided	Congenital long QT syndrome		no assertion provided	literature only	This variant has been reported in the following publications (PMID:12796536).