Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000631643 | SCV000752726 | likely benign | Long QT syndrome | 2024-01-13 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001420870 | SCV001623290 | likely benign | not specified | 2021-05-17 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1C c.5885G>A (p.Arg1962Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 279304 control chromosomes, predominantly at a frequency of 0.00071 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 71 fold of the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Timothy Syndrome phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.5885G>A has been reported in the literature in one individual affected with sudden unexplained death (Sanchez_2016). The report does not provide unequivocal conclusions about association of the variant with Timothy Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
| Ambry Genetics | RCV002354417 | SCV002649487 | likely benign | Cardiovascular phenotype | 2020-03-05 | 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. |
| Fulgent Genetics, |
RCV002485063 | SCV002800211 | likely benign | Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 | 2021-08-27 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003416060 | SCV004117446 | uncertain significance | CACNA1C-related disorder | 2023-01-26 | criteria provided, single submitter | clinical testing | The CACNA1C c.5885G>A variant is predicted to result in the amino acid substitution p.Arg1962Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.071% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-2797713-G-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |