Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000170689 | SCV000223242 | uncertain significance | not provided | 2016-04-21 | criteria provided, single submitter | clinical testing | The R947H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R947H variant was not observed with any significant frequency in approximately 5,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, the R947H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Furthermore, this substitution occurs at a position that is not conserved across species and in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. |
Center for Genomics, |
RCV003224182 | SCV003920048 | uncertain significance | Cardiac arrhythmia, ankyrin-B-related | 2021-03-30 | criteria provided, single submitter | clinical testing | ANK2 NM_001127493.1 exon 28 p.Arg947His (c.2840G>A): This variant has not been reported in the literature but is present in 0.04% (12/24094) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/4-114244917-G-A?dataset=gnomad_r2_1). This variant is present in ClinVar (Variation ID:190559). Evolutionary conservation for this variant is limited or unavailable; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |