ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.1778T>C (p.Ile593Thr)

dbSNP: rs28928904
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181818 SCV000234121 pathogenic not provided 2014-02-02 criteria provided, single submitter clinical testing p.Ile593Thr (ATA>ACA): c.1778 T>C in exon 7 of the KCNH2 gene (NM_000238.2)The I593T mutation in the KCNH2 gene has been reported in one individual with LQTS (reported as T1778C; Splawski I et al., 2000; www.cardiodb.org). I593T is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. Mutations in the same residue (I593K, I593R, I593V) and in nearby residues (G590V, G594D, K595E) have been reported in association with LQTS, supporting the functional importance of this region of the protein. Furthermore, the I593T mutation was not observed inapproximately 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.In summary, I593T in the KCNH2 gene is interpreted as a disease-causing mutation. The variant is found in LQT panel(s).
Ambry Genetics RCV004019003 SCV004891290 uncertain significance Cardiovascular phenotype 2020-07-31 criteria provided, single submitter clinical testing The c.1778T>C (p.I593T) alteration is located in exon 7 (coding exon 7) of the KCNH2 gene. This alteration results from a T to C substitution at nucleotide position 1778, causing the isoleucine (I) at amino acid position 593 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Cardiovascular Biomedical Research Unit, Royal Brompton & Harefield NHS Foundation Trust RCV000057985 SCV000089505 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:10973849). This is a literature report, and does not necessarily reflect the clinical interpretation of the Imperial College / Royal Brompton Cardiovascular Genetics laboratory.

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