Submissions for variant NM_000719.7(CACNA1C):c.372-15G>A

gnomAD frequency: 0.02977  dbSNP: rs55792866

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000253674	SCV000052070	benign	not specified	2019-06-11	criteria provided, single submitter	clinical testing	Variant summary: CACNA1C c.372-15G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.023 in 248948 control chromosomes in the gnomAD database, including 99 homozygotes. The observed variant frequency is approximately 2343-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in CACNA1C causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.372-15G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics, part of Exact Sciences	RCV000253674	SCV000305447	benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV001610297	SCV001834321	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Invitae	RCV002054480	SCV002416278	benign	Long QT syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002496445	SCV002810216	benign	Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8	2021-09-01	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000253674	SCV001920844	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000253674	SCV001926562	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000253674	SCV001957092	benign	not specified		no assertion criteria provided	clinical testing