ClinVar Miner

Submissions for variant NM_181798.1(KCNQ1):c.1305-2A>G (rs878854350)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital RCV000234808 SCV000240223 pathogenic Long QT syndrome 1 2011-01-01 criteria provided, single submitter research
Invitae RCV000456381 SCV000543298 likely pathogenic Long QT syndrome 2019-05-07 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 13 of the KCNQ1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in a individual affected with a recessive form of long QT syndrome (PMID: 27041150). ClinVar contains an entry for this variant (Variation ID: 207973). Algorithms developed to predict the effect of sequence changes on mRNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, donor and acceptor splice site variants are typically truncating (PMID: 16199547), and truncating variants in KCNQ1 are known to be pathogenic (PMID: 19862833). However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000621754 SCV000736404 likely pathogenic Cardiovascular phenotype 2020-08-11 criteria provided, single submitter clinical testing The c.1686-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 14 in the KCNQ1 gene. This variant was reported in an individual with Romano-Ward syndrome, who was a compound heterozygote with an additional KCNQ1 alteration (p.R533W, c.1597C>T); the proband's father had a QTc of 415ms and was reported to be heterozygous for the c.1686-2A>G variant (Vyas B et al. Am. J. Med. Genet. A, 2016 Jun;170:1510-9). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic mutation.
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000786150 SCV000924825 pathogenic not provided 2017-03-09 no assertion criteria provided provider interpretation

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