Submissions for variant NM_000719.7(CACNA1C):c.5549A>C (p.Glu1850Ala)

gnomAD frequency: 0.00001  dbSNP: rs375846068

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817497	SCV000958061	uncertain significance	Long QT syndrome	2024-10-29	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1850 of the CACNA1C protein (p.Glu1850Ala). This variant is present in population databases (rs375846068, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 660329). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CACNA1C protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV000994776	SCV001148537	uncertain significance	not provided	2018-04-01	criteria provided, single submitter	clinical testing
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV001089532	SCV001244886	uncertain significance	Timothy syndrome	2019-09-26	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002478907	SCV002792076	uncertain significance	Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8	2021-07-29	criteria provided, single submitter	clinical testing