Submissions for variant NM_000218.3(KCNQ1):c.794C>T (p.Thr265Ile)

dbSNP: rs199472724

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000182115	SCV000234418	pathogenic	not provided	2012-06-28	criteria provided, single submitter	clinical testing	p.Thr265Ile (ACC>ATC): c.794 C>T in exon 6 of the KCNQ1 gene (NM_000218.2). The Thr265Ile mutation in the KCNQ1 gene has been reported previously in association with LQTS, and this mutation was absent in 100 control alleles (Chung S et al., 2007; Yang T et al., 2009). Chung et al. identified the Thr265Ile mutation in a 40 year-old female with LQTS and Wang et al. subsequently identified the mutation in this patient's father and three children who all had symptoms and/or QT prolongation. The NHLBI ESP Exome Variant Server reports Thr265Ile was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Thr265Ile results in a non-conservative amino acid substitution of a neutral, polar Threonine with a non-polar Isoleucine at a residue that is conserved across mammal species. In addition, mutations in nearby codons (Leu262Val, Leu266Pro) have also been reported in association with LQTS, supporting the functional importance of this region of the protein. In summary, Thr265Ile in the KCNQ1 gene is interpreted to be a disease-causing mutation. The variant is found in LQT panel(s).
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust	RCV000057762	SCV000089281	not provided	Congenital long QT syndrome		no assertion provided	literature only	This variant has been reported as associated with Long QT syndrome in the following publications (PMID:17905336;PMID:19808498). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.