ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.1867C>A (p.Pro623Thr) (rs199473014)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756285 SCV000884050 uncertain significance not provided 2017-08-07 criteria provided, single submitter clinical testing The p.Pro963Thr variant (rs199473014) was reported in one patient in a cohort of ~400, and determined as one of C-terminal variants in KCNH2 with elevated allele frequency in Long-QT cases compared to controls (Kapa, 2009). Further analysis using a combination of prediction tools concluded this variant might be benign (Giudicessi, 2012). This variant is listed in the Genome Aggregation Database (gnomAD) with an overall population frequency of 0.0009 percent (identified on 2 out of 214,534 chromosomes). It is also reported in ClinVar (Variation ID: 67449) without any clinical significance. The proline at position 963 is moderately conserved and computational analyses of the effects of the p.Pro963Thr variant on protein structure and function provide conflicting results (SIFT: tolerated, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Pro963Thr variant with certainty.
Cardiovascular Biomedical Research Unit,Royal Brompton & Harefield NHS Foundation Trust RCV000058176 SCV000089696 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:19841300). 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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