ClinVar Miner

Submissions for variant NM_020361.5(CPA6):c.619C>G (p.Gln207Glu) (rs35993949)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Claritas Genomics RCV000449549 SCV000537840 uncertain significance Global developmental delay 2017-02-21 criteria provided, single submitter clinical testing
GeneDx RCV000711314 SCV000581747 uncertain significance not provided 2018-07-31 criteria provided, single submitter clinical testing The Q207E variant in the CPA6 gene has been previously reported in the heterozygous state in two individuals with epilepsy who were also heterozygous for the G267R variant (Allen et al., 2016; Sapio et al., 2012). In one of these individuals, the variants were determined to be on the same CPA6 allele (in cis) and inherited from the individual's mother, who was reported to have unexplained epilepsy but not epileptic encephalopathy, while in the other individual, the phase of the two variants was not confirmed as parents were not tested (Allen et al., 2016; Sapio et al., 2012). Although not present in the homozygous state, the Q207E variant is observed in 149/66606 (0.22%) alleles from individuals of European Non-Finnish background and in 4/10404 (0.18%) alleles from individuals of African American background in the ExAC dataset (Lek et al., 2016). Additionally, it has been identified in 94/48620 (0.19%) alleles from presumably healthy individuals tested at GeneDx. The Q207E variant is a semi-conservative amino acid substitution that occurs at a position that is conserved across species. One in vitro functional study concluded that this variant significantly reduces enzyme activity; however, additional studies are needed to determine whether loss-of-function variants in CPA6 increases the risk of seizures (Sapio et al., 2012). We interpret Q207E as a variant of uncertain significance.
Invitae RCV001085402 SCV000651981 likely benign Febrile seizures, familial, 11 2019-12-31 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000711314 SCV000708910 uncertain significance not provided 2018-05-25 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000711314 SCV000841655 uncertain significance not provided 2018-09-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000445558 SCV001325947 uncertain significance Epilepsy, familial temporal lobe, 5 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
OMIM RCV000445558 SCV000537137 pathogenic Epilepsy, familial temporal lobe, 5 2012-12-14 no assertion criteria provided literature only
Bioinformatics Core,Luxembourg Center for Systems Biomedicine RCV000656015 SCV000588291 pathogenic Rolandic epilepsy 2017-01-01 no assertion criteria provided case-control CAADphred>15
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003970 SCV001161979 likely pathogenic Seizures; Focal seizures; Menstrual irregularities; Confusion; Palpitations; Periventricular gray matter heterotopia; Abnormal emotion/affect behavior no assertion criteria provided research

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