ClinVar Miner

Submissions for variant NM_004980.4(KCND3):c.1348C>T (p.Leu450Phe) (rs150401343)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000618307 SCV000738231 uncertain significance Cardiovascular phenotype 2017-11-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
CeGaT Praxis fuer Humangenetik Tuebingen RCV000415916 SCV000493333 likely pathogenic not provided 2016-08-31 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000172842 SCV000595296 likely pathogenic Brugada syndrome 9 2016-04-09 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000172842 SCV000746546 likely pathogenic Brugada syndrome 9 2017-12-03 criteria provided, single submitter clinical testing
Invitae RCV000552635 SCV000640057 uncertain significance Spinocerebellar ataxia 19 2018-02-01 criteria provided, single submitter clinical testing This sequence change replaces leucine with phenylalanine at codon 450 of the KCND3 protein (p.Leu450Phe). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs150401343, ExAC 0.02%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been reported in an individual affected with Brugada syndrome and in an individual affected with idiopathic cerebellar gait ataxia (PMID: 21349352, 23963749). ClinVar contains an entry for this variant (Variation ID: 192253). Experimental studies have shown that this missense change increases the channel current density, indicating that it causes a gain of function (PMID: 21349352, 26016905). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000172842 SCV000223808 pathogenic Brugada syndrome 9 2011-07-01 no assertion criteria provided literature only

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