ClinVar Miner

Submissions for variant NM_000238.4(KCNH2):c.2729_2744del (p.Pro910fs)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002431345 SCV002741485 pathogenic Cardiovascular phenotype 2018-01-09 criteria provided, single submitter clinical testing The c.2729_2744del16 pathogenic mutation, located in coding exon 12 of the KCNH2 gene, results from a deletion of 16 nucleotides at nucleotide positions 2729 to 2744, causing a translational frameshift with a predicted alternate stop codon (p.P910Qfs*59). In a study of long QT syndrome clinical genetic testing, this alteration was reported in one patient; however, clinical details were limited (Kapplinger JD et al. Heart Rhythm, 2009 Sep;6:1297-303). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV003533266 SCV004294705 pathogenic Long QT syndrome 2023-02-11 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1795256). This premature translational stop signal has been observed in individual(s) with clinical features of KCNH2-related disorders (PMID: 19716085). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro910Glnfs*59) in the KCNH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNH2 are known to be pathogenic (PMID: 10973849, 19862833).
Clinical Genetics Laboratory, Skane University Hospital Lund RCV004697229 SCV005197397 likely pathogenic not provided 2022-05-27 criteria provided, single submitter clinical testing

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