Total submissions: 4
            
    | Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment | 
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics | RCV002514138 | SCV003525173 | pathogenic | not provided | 2024-12-24 | criteria provided, single submitter | clinical testing | This variant, c.1208_1209insGGG, results in the insertion of 1 amino acid(s) of the CACNA1D protein (p.Gly403dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs751923238, gnomAD 0.006%). This variant has been observed in individual(s) with autosomal recessive sinoatrial node dysfunction and deafness (PMID: 21131953, 30498240). It has also been observed to segregate with disease in related individuals. This variant is also known as p.403_404insGly. ClinVar contains an entry for this variant (Variation ID: 39709). For these reasons, this variant has been classified as Pathogenic. | 
| Neuberg Centre For Genomic Medicine, | RCV000032914 | SCV004048083 | pathogenic | Sinoatrial node dysfunction and deafness | criteria provided, single submitter | clinical testing | The variant c.1208_1209insGGG (p.Gly403dup) in CACNA1D gene has been reported previously in patients affected with sinoatrial node dysfunction and deafness that segregated with disease in the family (Baig et al., 2011). This variant has been reported to the ClinVar database as Pathogenic. The p.Gly403dup variant is reported with the allele frequency (0.0007%) in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This p.Gly403dup causes duplication of amino acid Glycine at postion 403. Alleles of single nucleotide polymorphisms (SNPs) from the CACNA1D locus have revealed the same c.1208_1209insGGG associated haplotype in three families, compatible with a founder mutation inherited from a common ancestor (Baig et al., 2011). For these reasons, this variant has been classified as Pathogenic. | |
| OMIM | RCV000032914 | SCV000056686 | pathogenic | Sinoatrial node dysfunction and deafness | 2011-01-01 | no assertion criteria provided | literature only | |
| University of Washington Center for Mendelian Genomics, | RCV000032914 | SCV001480018 | likely pathogenic | Sinoatrial node dysfunction and deafness | no assertion criteria provided | research |