Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000685235 | SCV000812708 | uncertain significance | Atrial fibrillation, familial, 7 | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 87 of the KCNA5 protein (p.Arg87Gln). This variant is present in population databases (rs71537801, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with atrial fibrillation and Brugada syndrome (PMID: 18209767, 26220970). ClinVar contains an entry for this variant (Variation ID: 565628). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects KCNA5 function (PMID: 16411137). 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 |
RCV001823160 | SCV002072829 | uncertain significance | not provided | 2022-01-14 | criteria provided, single submitter | clinical testing | Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#565628); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; In vitro functional studies in CHO cells suggest the R87Q variant may impact channel function, however, it is not reproduced when expressed in the HEK 293 cells (Plante et al., 2006); additional studies are needed to clarify the functional effect of this variant in vivo; This variant is associated with the following publications: (PMID: 16411137, 26220970, 18209767, 27535533, 26582918) |
Fulgent Genetics, |
RCV000685235 | SCV002787703 | uncertain significance | Atrial fibrillation, familial, 7 | 2021-08-20 | criteria provided, single submitter | clinical testing |