ClinVar Miner

Submissions for variant NM_001378969.1(KCND3):c.641A>G (p.Lys214Arg)

gnomAD frequency: 0.00034  dbSNP: rs142744204
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208485 SCV000263968 likely benign not specified 2014-12-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000249346 SCV000320287 likely benign Cardiovascular phenotype 2023-12-07 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000558965 SCV000640063 uncertain significance Spinocerebellar ataxia type 19/22 2024-01-13 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 214 of the KCND3 protein (p.Lys214Arg). This variant is present in population databases (rs142744204, gnomAD 0.03%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with atrial fibrillation, an episodic gait disorder or Brugada syndrome (PMID: 21349352, 22402074, 25410959, 26220970, 29482223). ClinVar contains an entry for this variant (Variation ID: 222665). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCND3 protein function with a negative predictive value of 80%. 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.
GeneDx RCV001555788 SCV001777255 likely benign not provided 2021-06-17 criteria provided, single submitter clinical testing Reported in a patient with features of cerebellar ataxia referred for whole exome sequencing; however, this variant was inherited from an unaffected mother (Coutelier et al., 2018); Reported in one ostensibly healthy control individual and in association with atrial fibrillation (Giudicessi et al., 2011; Mann et al., 2012); Published functional studies demonstrate no damaging effect (Mann et al., 2012); This variant is associated with the following publications: (PMID: 26220970, 23838598, 25175087, 25410959, 29482223, 22402074, 21349352)
Institute of Human Genetics, University Hospital of Duesseldorf RCV000558965 SCV003803728 uncertain significance Spinocerebellar ataxia type 19/22 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001555788 SCV001927243 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001555788 SCV001973320 likely benign not provided no assertion criteria provided clinical testing

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