Submissions for variant NM_000719.7(CACNA1C):c.966C>T (p.His322=)

gnomAD frequency: 0.00042  dbSNP: rs112539787

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124070	SCV000167479	benign	not specified	2012-05-07	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV001087219	SCV000562921	benign	Long QT syndrome	2024-01-25	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586377	SCV000697558	benign	not provided	2017-04-17	criteria provided, single submitter	clinical testing	Variant summary: The CACNA1C c.966C>T (p.His322His) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 85/121084 control chromosomes (1 homozygote) at a frequency of 0.000702, which is approximately 70 times the estimated maximal expected allele frequency of a pathogenic CACNA1C variant (0.00001), suggesting this variant is likely a benign polymorphism. This variant has been reported in a cohort of Long QT patients with comparable MAF in controls. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Ambry Genetics	RCV000618328	SCV000735380	likely benign	Cardiovascular phenotype	2016-03-03	criteria provided, single submitter	clinical testing	Synonymous alterations with insufficient evidence to classify as benign
Ambry Genetics	RCV000719849	SCV000850720	likely benign	History of neurodevelopmental disorder	2016-03-03	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: Synonymous alterations with insufficient evidence to classify as benign
PreventionGenetics, part of Exact Sciences	RCV003952643	SCV004771923	likely benign	CACNA1C-related disorder	2023-11-08	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000124070	SCV001921460	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000586377	SCV001965348	likely benign	not provided		no assertion criteria provided	clinical testing