ClinVar Miner

Submissions for variant NM_172057.2(KCNH2):c.2132+2T>C (rs1057518169)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000413963 SCV000491607 pathogenic not provided 2016-10-27 criteria provided, single submitter clinical testing Although the c.3152+2 T>C variant in the KCNH2 gene has not been reported as a pathogenic variant or as a benign variant to our knowledge, it destroys the canonical splice donor site in intron 13 and is predicted to cause abnormal gene splicing. This variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Multiple other splice site variants in the KCNH2 gene have been reported in HGMD in association with LQTS (Stenson et al., 2014). Additionally, two pathogenic splice site variants in the KCNH2 gene, occurring in the adjacent nucleotide (c.3152+1 G>A, c.3152+1 G>T), have been reported at GeneDx in association with LQTS, supporting the functional importance of this canonical splice donor site. Furthermore, the c.3152+2 T>C variant was not observed in approximately 5,800 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project (average read depth 6x).In summary, c.3152+2 T>C in the KCNH2 gene is interpreted as a pathogenic variant.

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