ClinVar Miner

Submissions for variant NM_023035.3(CACNA1A):c.4186G>A (p.Val1396Met) (rs794727411)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000176622 SCV000228310 pathogenic not provided 2017-08-31 criteria provided, single submitter clinical testing
GeneDx RCV000176622 SCV000322140 pathogenic not provided 2021-02-16 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29056246, 27959697, 28007337, 30283815, 31487502, 31468518, 29100083, 33258288, 33425808)
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000604986 SCV000731256 likely pathogenic Epileptic encephalopathy, early infantile, 42 2017-12-14 criteria provided, single submitter research
Ambry Genetics RCV000623848 SCV000741273 pathogenic Inborn genetic diseases 2020-05-27 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000604986 SCV000784524 likely pathogenic Epileptic encephalopathy, early infantile, 42 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000662176 SCV000784525 likely pathogenic Migraine 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000662177 SCV000784526 likely pathogenic Episodic ataxia type 2 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000662178 SCV000784527 likely pathogenic Spinocerebellar ataxia type 6 2018-03-05 criteria provided, single submitter clinical testing
Genomic Research Center,Shahid Beheshti University of Medical Sciences RCV000662179 SCV000784528 likely pathogenic Familial hemiplegic migraine type 1 2018-03-05 criteria provided, single submitter clinical testing
Invitae RCV001061471 SCV001226215 pathogenic Episodic ataxia type 2; Epileptic encephalopathy, early infantile, 42 2020-06-16 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 1393 of the CACNA1A protein (p.Val1393Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with ataxia, tremor, developmental delay, and epilepsy (PMID: 28007337, 30283815) as well as individuals with epileptic encephalopathy (PMID: 29056246, 29100083). In at least one individual the variant was observed to be de novo. It is also known as NM_023035.2:c.4186G>A (p.V1396M) in the literature. ClinVar contains an entry for this variant (Variation ID: 195935). This variant has been reported to affect CACNA1A protein function (PMID: 31468518). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000662179 SCV001369060 likely pathogenic Familial hemiplegic migraine type 1 2019-05-07 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PP3,PP4.
Baylor Genetics RCV000604986 SCV001519691 pathogenic Epileptic encephalopathy, early infantile, 42 2020-06-03 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Pediatrics, MediClubGeorgia RCV000662177 SCV001571711 pathogenic Episodic ataxia type 2 2021-04-25 criteria provided, single submitter clinical testing This variant has previously been described as disease causing for Ataxia, ClinVar lists this variant as pathogenic (Variation ID: 195935) and uncertain (Variation ID: 195935) and likely pathogenic (ID: 195935). This variant is absent parents. PolyPhen: Probably damaging ; Align-GVGD: C0; MutationTaster: Disease causing Conservation_nt: high; Conservation_aa: weak; This variant is absent in population databases.
Mayo Clinic Laboratories, Mayo Clinic RCV000176622 SCV001713787 pathogenic not provided 2019-05-20 criteria provided, single submitter clinical testing
Baylor Genetics RCV000415108 SCV000328711 likely pathogenic Episodic ataxia type 2; Familial hemiplegic migraine type 1 2014-10-16 no assertion criteria provided clinical testing Our laboratory reported dual molecular diagnoses in CACNA1A (NM_001174080.1, c.4177G>A) and SLC26A1 (NM_022042.2, c.1487T>G) in one individual with reported features of intractable epilepsy, global developmental delay, tremor, ataxia, hyperlipidemia, growth hormone deficiency, and stable right optic nerve glioma. Missense and truncating variants in CACNA1A have been reported in patients with epilepsy (PMID:18940563;PMID:21703448)
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000176622 SCV001929399 likely pathogenic not provided no assertion criteria provided clinical testing

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