ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.322A>G (p.Ile108Val)

dbSNP: rs1599294284
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000793236 SCV000932579 likely pathogenic Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 108 of the CACNA1A protein (p.Ile108Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with CACNA1A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 640253). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1A protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics RCV001089748 SCV001245235 likely pathogenic Developmental and epileptic encephalopathy, 42 2020-02-14 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001089748 SCV002028293 likely pathogenic Developmental and epileptic encephalopathy, 42 2021-11-26 criteria provided, single submitter clinical testing
MGZ Medical Genetics Center RCV002290431 SCV002581074 likely pathogenic Episodic ataxia type 2 2022-07-22 criteria provided, single submitter clinical testing
GenomeConnect - Brain Gene Registry RCV003987706 SCV004804546 not provided Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42 no assertion provided phenotyping only Variant classified as Uncertain significance and reported on 11-10-2022 by Invitae . Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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