Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001550689 | SCV001771062 | uncertain significance | not provided | 2023-10-26 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV001550689 | SCV002121823 | uncertain significance | not provided | 2025-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 261 of the ALPK3 protein (p.Ser261Pro). This variant is present in population databases (rs750401200, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with ALPK3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1190103). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 | RCV002414260 | SCV002669582 | uncertain significance | Cardiovascular phenotype | 2022-10-27 | criteria provided, single submitter | clinical testing | The p.S261P variant (also known as c.781T>C), located in coding exon 2 of the ALPK3 gene, results from a T to C substitution at nucleotide position 781. The serine at codon 261 is replaced by proline, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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. |
| Revvity Omics, |
RCV003492264 | SCV004238578 | uncertain significance | Cardiomyopathy, familial hypertrophic 27 | 2023-02-14 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics Laboratory, |
RCV003492264 | SCV005062013 | uncertain significance | Cardiomyopathy, familial hypertrophic 27 | 2021-07-26 | criteria provided, single submitter | clinical testing | The p.Ser261Pro variant in the ALPK3gene has not been previously reported in association with disease. This variant has been identified in 10/35,430 Latino/Admixed American chromosomes (48/282,876 chromosomes overall) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. The serine at position 261 is fairly evolutionarily conservedin mammals, although 1 mammalian species (shrew) has a proline at this position. Computational tools predict that the p.Ser261Pro variant does not impact protein function; however, the accuracy of in silicoalgorithms is limited.•These data were assessed using the ACMG/AMP variant interpretation guidelines. In summary, the significance of thep.Ser261Provariant is uncertain. Additional information is needed to resolve the significance of this variant. [ACMG evidence codes used: BP4] |