Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000617554 | SCV000737595 | likely benign | Cardiovascular phenotype | 2022-04-07 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Invitae | RCV000631714 | SCV000752801 | uncertain significance | Long QT syndrome | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 585 of the CACNA1C protein (p.Val585Met). This variant is present in population databases (rs763738559, gnomAD 0.007%). 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: 519274). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1C protein function. 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. |
Gene |
RCV001591382 | SCV001823820 | uncertain significance | not provided | 2020-09-30 | criteria provided, single submitter | clinical testing | Has been reported in an individual with sudden unexplained death at 36 years of age, and cardiac findings on autopsy showed interstitial fibrosis and myocyte hypertrophy (Shanks et al., 2018); however, a frameshift variant in the A-band of the TTN gene was also identified and no family history or segregation details were reported.; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29915097) |
Fulgent Genetics, |
RCV002483715 | SCV002791278 | uncertain significance | Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 | 2021-08-18 | criteria provided, single submitter | clinical testing | |
Clinical Genetics, |
RCV001591382 | SCV001921611 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001591382 | SCV001971340 | uncertain significance | not provided | no assertion criteria provided | clinical testing |