ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.5996C>T (p.Thr1999Ile)

gnomAD frequency: 0.00002  dbSNP: rs532551057
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000232392 SCV000285601 likely benign Long QT syndrome 2024-01-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619708 SCV000737410 uncertain significance Cardiovascular phenotype 2017-03-02 criteria provided, single submitter clinical testing The p.T1999I variant (also known as c.5996C>T), located in coding exon 46 of the CACNA1C gene, results from a C to T substitution at nucleotide position 5996. The threonine at codon 1999 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002503893 SCV002817034 uncertain significance Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 2021-10-29 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV003389323 SCV004101481 uncertain significance Long qt syndrome 8 criteria provided, single submitter clinical testing The missense variant c.6245C>T (p.Thr2082Ile) in CACNA1C gene has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. It has not been reported in affected individuals. The p.Thr2082Ile variant is reported with the allele frequency (0.005%) in the gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The amino acid Thr at position 2082 is changed to a Ile changing protein sequence and it might alter its composition and physico-chemical properties. In silico tools predict the variant to be tolerated. The residue is conserved across species. The amino acid change p.Thr2082Ile in CACNA1C is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS)
KardioGenetik, Herz- und Diabeteszentrum NRW RCV003389323 SCV004809109 uncertain significance Long qt syndrome 8 2024-02-15 criteria provided, single submitter clinical testing

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