Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004297926 | SCV003954664 | uncertain significance | not specified | 2023-04-24 | criteria provided, single submitter | clinical testing | The c.746G>A (p.R249H) alteration is located in exon 5 (coding exon 4) of the ATP2B2 gene. This alteration results from a G to A substitution at nucleotide position 746, causing the arginine (R) at amino acid position 249 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005102562 | SCV005776920 | uncertain significance | not provided | 2024-04-06 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 249 of the ATP2B2 protein (p.Arg249His). This variant is present in population databases (rs200591536, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with ATP2B2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2523714). 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 ATP2B2 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. |