Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000547612 | SCV000627561 | uncertain significance | Long QT syndrome | 2020-08-14 | 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 disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with methionine at codon 1749 of the CACNA1C protein (p.Val1749Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. |
Prevention |
RCV003403258 | SCV004105560 | uncertain significance | CACNA1C-related disorder | 2023-07-31 | criteria provided, single submitter | clinical testing | The CACNA1C c.5245G>A variant is predicted to result in the amino acid substitution p.Val1749Met. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |