ClinVar Miner

Submissions for variant NM_001112741.1(KCNC1):c.959G>A (p.Arg320His) (rs727502818)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000149909 SCV000655548 pathogenic Epilepsy, progressive myoclonic 7 2019-09-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 320 of the KCNC1 protein (p.Arg320His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as a recurrent de novo mutation in many individuals affected with progressive myoclonus epilepsy (PME) (PMID: 25401298, 28380698). It has also been reported to segregate with PME in an affected family (PMID: 28380698). ClinVar contains an entry for this variant (Variation ID: 162519). In experimental studies, this missense change results in loss of KCNC1 protein function and a dominant-negative effect on wild-type Kv3.1 channels (PMID: 25401298, 28380698). In summary, this variant is a rare missense change with a dominant-negative effect on protein function. It has also been reported to be a recurrent de novo mutation in individuals with KCNC1-related disease. For these reasons, this variant has been classified as Pathogenic.
Undiagnosed Diseases Network,NIH RCV000149909 SCV000837691 pathogenic Epilepsy, progressive myoclonic 7 2018-02-07 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000149909 SCV000893873 pathogenic Epilepsy, progressive myoclonic 7 2018-10-31 criteria provided, single submitter clinical testing
Mendelics RCV000149909 SCV001138241 pathogenic Epilepsy, progressive myoclonic 7 2019-05-28 criteria provided, single submitter clinical testing
OMIM RCV000149909 SCV000196760 pathogenic Epilepsy, progressive myoclonic 7 2015-01-01 no assertion criteria provided literature only

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