ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.202G>A (p.Ala68Thr)

gnomAD frequency: 0.00014  dbSNP: rs752000790
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000761812 SCV000223403 uncertain significance not provided 2018-12-10 criteria provided, single submitter clinical testing p.Ala68Thr (GCT>ACT): c.202 G>A in exon 2 of the CACNA1C gene (NM_000719.6). The A68T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A68T variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A68T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. No missense mutations in nearby residues have been reported in association with LQTS, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LQT panel(s).
Illumina Laboratory Services, Illumina RCV000357698 SCV000377588 uncertain significance Timothy syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000262517 SCV000377589 uncertain significance Brugada syndrome 2016-06-14 criteria provided, single submitter clinical testing
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues RCV000357698 SCV000805139 uncertain significance Timothy syndrome 2018-01-31 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000761812 SCV000892013 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781192 SCV000919075 likely benign not specified 2017-11-06 criteria provided, single submitter clinical testing Variant summary: The CACNA1C c.202G>A (p.Ala68Thr) variant involves the alteration of a conserved nucleotide and 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO and MutationTaster not captured here due to low reliability index and p-value, respectively). This variant was found in 41/261782 control chromosomes at a frequency of 0.0001566, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000309 (37/119594). This frequency is about 31 times the estimated maximal expected allele frequency of a pathogenic CACNA1C variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. This variant has been reported in multiple affected individuals without strong evidence for casualty. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, without evidence for independent evaluation. Taken together, this variant is classified as likely benign.
Invitae RCV000794589 SCV000934007 likely benign Long QT syndrome 2024-01-27 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000357698 SCV001367871 uncertain significance Timothy syndrome 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3,PP4.
Ambry Genetics RCV002415722 SCV002721833 benign Cardiovascular phenotype 2021-12-13 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.