ClinVar Miner

Submissions for variant NM_172056.2(KCNH2):c.1048del (p.Ala350fs) (rs1064793523)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480550 SCV000566332 likely pathogenic not provided 2017-04-26 criteria provided, single submitter clinical testing Although the c.1048delG variant in the KCNH2 gene has not been reported to our knowledge, thisdeletion causes a shift in reading frame starting at codon Alanine350, changing it to a Leucine, andcreating a premature stop codon at position 10 of the new reading frame, denoted p.Ala350LeufsX10. Thisdeletion is expected to result in either an abnormal, truncated protein product or loss of protein from thisallele through nonsense-mediated mRNA decay. Other frameshift variants in the KCNH2 gene havebeen reported in HGMD in association with LQTS (Stenson P et al., 2014). Furthermore, the c.1048delGvariant was not observed in approximately 6500 individuals of European and African American ancestry inthe NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populationsBased on currently available evidence, c.1048delG is a strong candidate for a pathogenic variant. However, the possibility it is a rare benign variant cannot be excluded.

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