ClinVar Miner

Submissions for variant NM_000218.3(KCNQ1):c.200_210del (p.Pro67fs)

dbSNP: rs1435990592
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519994 SCV000617085 pathogenic not provided 2021-06-03 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Identified in patients with Long QT syndrome referred for testing at GeneDx and in the published literature (Kapplinger et al., 2009).; Not observed at significant frequency in large population cohorts (Lek et al., 2016) This variant is associated with the following publications: (PMID: 19716085, 27535533, 26582918)
Invitae RCV000552160 SCV000627392 pathogenic Long QT syndrome 2023-07-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro67Argfs*214) in the KCNQ1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ1 are known to be pathogenic (PMID: 9323054, 19862833). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with long QT syndrome (PMID: 19716085). ClinVar contains an entry for this variant (Variation ID: 449221). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV000619399 SCV000737662 pathogenic Cardiovascular phenotype 2018-09-13 criteria provided, single submitter clinical testing The c.200_210del11 pathogenic mutation, located in coding exon 1 of the KCNQ1 gene, results from a deletion of 11 nucleotides at nucleotide positions 200 to 210, causing a translational frameshift with a predicted alternate stop codon (p.P67Rfs*214). In a study of long QT syndrome clinical genetic testing, this alteration (also described as S66fs+213X) 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.
AiLife Diagnostics, AiLife Diagnostics RCV000519994 SCV002501679 pathogenic not provided 2021-12-30 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002490900 SCV002776724 likely pathogenic Atrial fibrillation, familial, 3; Beckwith-Wiedemann syndrome; Long QT syndrome 1; Jervell and Lange-Nielsen syndrome 1; Short QT syndrome type 2 2021-12-05 criteria provided, single submitter clinical testing
Molecular Genetics Laboratory - Cardiogenetics, CHU de Nantes RCV003319366 SCV004024210 pathogenic Long QT syndrome 1 2023-08-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004537868 SCV004750700 pathogenic KCNQ1-related disorder 2024-01-26 criteria provided, single submitter clinical testing The KCNQ1 c.200_210del11 variant is predicted to result in a frameshift and premature protein termination (p.Pro67Argfs*214). This variant has been reported to be causative for long QT syndrome (described as 200_210delCGGCCGCGCCC (S66fs+213X) in Table S1, Kapplinger et al. 2009. PubMed ID: 19716085). This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in KCNQ1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000519994 SCV000924832 pathogenic not provided 2016-10-12 no assertion criteria provided provider interpretation

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