Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001069724 | SCV001234914 | uncertain significance | Long QT syndrome | 2021-05-29 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CACNA1C-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with serine at codon 1309 of the CACNA1C protein (p.Thr1309Ser). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and serine. |
| Neuberg Supratech Reference Laboratories Pvt Ltd, |
RCV003339458 | SCV004047192 | uncertain significance | Long qt syndrome 8 | criteria provided, single submitter | clinical testing | The missense variant in c.3926C>G(p.Thr1309Ser) in CACNA1C gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is novel (not in any individual) in gnomAD and 1000 genome. This variant has been reported to the ClinVar database as Uncertain significance. The amino acid Thr at position 1309 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as uncertain significance. |