Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000723717 | SCV000111160 | uncertain significance | not provided | 2013-10-16 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000723717 | SCV000329182 | uncertain significance | not provided | 2018-01-16 | criteria provided, single submitter | clinical testing | The c.3969 C>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.3969 C>T variant was not observed with any significant frequency in approximately 6,500 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 c.3969 C>T variant results in a synonymous amino acid substitution, I1323I, and in silico splice prediction programs are unable to predict whether this nucleotide substitution has an impact on normal gene splicing. Additionally, the majority of variants in the CACNA1C gene are missense changes (Stenson et al., 2014), indicating haploinsufficiency of CACNA1C may not be sufficient to cause disease. Nevertheless, this substitution occurs at a position that is conserved across species. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Invitae | RCV001083964 | SCV000627542 | likely benign | Long QT syndrome | 2023-12-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781193 | SCV000919076 | benign | not specified | 2017-11-06 | criteria provided, single submitter | clinical testing | Variant summary: The CACNA1C c.3969C>T (p.Ile1323Ile) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 15/277196 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000118 (15/126706). This frequency is about 12 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. The variant has been reported in the literature, without strong evidence for causality. Multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, without evidence for independent evaluation. Taken together, this variant is classified as benign. |
Ambry Genetics | RCV002354275 | SCV002623064 | likely benign | Cardiovascular phenotype | 2021-02-25 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |