Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001213724 | SCV001385373 | uncertain significance | Long QT syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 78 of the KCNQ1 protein (p.Asp78Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of long QT syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 943522). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on KCNQ1 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. |
| Ambry Genetics | RCV003380885 | SCV004088818 | uncertain significance | Cardiovascular phenotype | 2023-07-27 | criteria provided, single submitter | clinical testing | The p.D78A variant (also known as c.233A>C), located in coding exon 1 of the KCNQ1 gene, results from an A to C substitution at nucleotide position 233. The aspartic acid at codon 78 is replaced by alanine, an amino acid with dissimilar properties. This variant has been detected in individuals undergoing genetic testing for epilepsy and unspecifiied cardiovascular indications; however, details were limited (Li X et al. Ann Hum Genet, 2020 Mar;84:161-168). This amino acid position is not conserved on limited sequence alignment. 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. |