Submissions for variant NM_000719.7(CACNA1C):c.2449C>T (p.Pro817Ser)

gnomAD frequency: 0.00279  dbSNP: rs112532048

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001080618	SCV000262441	benign	Long QT syndrome	2024-01-31	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000079284	SCV000335662	likely benign	not specified	2017-06-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620022	SCV000735962	benign	Cardiovascular phenotype	2017-12-27	criteria provided, single submitter	clinical testing	Does not segregate with disease in family study (genes with incomplete penetrance);In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Ambry Genetics	RCV000718458	SCV000849321	benign	History of neurodevelopmental disorder	2017-12-27	criteria provided, single submitter	clinical testing	Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification,Does not segregate with disease in family study (genes with incomplete penetrance)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001668189	SCV000885136	benign	not provided	2023-10-13	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852662	SCV000995368	benign	Hypertrophic cardiomyopathy	2018-02-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001668189	SCV001891713	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 24439875)
CeGaT Center for Human Genetics Tuebingen	RCV001668189	SCV002544990	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	CACNA1C: PP2, BS1
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470758	SCV002767743	likely benign	Timothy syndrome	2020-10-19	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as likely benign. Following criteria are met: 0101 - Gain of function is a known mechanism of disease in this gene and is associated with Long QT syndrome 8 (MIM #618447), and Timothy syndrome (MIM#601005). Missense variants result in loss of channel inactivation, and increased current (OMIM, PMID: 25260352). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to serine. (I) 0251 - This variant is heterozygous. (I) 0308 - Population frequency for this variant is out of keeping with known incidence of Timothy syndrome and LQTS. Variant is present in gnomAD (503 heterozygotes (v2), 1 homozygote (v3)). (SB) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0805 - This variant has strong previous evidence of being benign in unrelated individuals. This variant has one likely benign and five benign entries in ClinVar. (SB) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
PreventionGenetics, part of Exact Sciences	RCV003925044	SCV004743357	benign	CACNA1C-related disorder	2019-05-17	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001668189	SCV001928608	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000079284	SCV001956494	benign	not specified		no assertion criteria provided	clinical testing