Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001555536 | SCV001776974 | uncertain significance | not provided | 2023-05-18 | criteria provided, single submitter | clinical testing | Identified in patients with cardiomyopathy in the published literature (van Lint et al., 2019; Herkert et al., 2020); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 32480058, 30847666) |
| Labcorp Genetics |
RCV001555536 | SCV002273396 | uncertain significance | not provided | 2023-12-15 | 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 1215 of the ALPK3 protein (p.Arg1215His). This variant is present in population databases (rs201993684, gnomAD 0.08%). This missense change has been observed in individual(s) with dilated cardiomyopathy or hypertrophic cardiomyopathy (PMID: 30847666, 32480058). ClinVar contains an entry for this variant (Variation ID: 1193213). 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 disruptive. 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 | RCV002458525 | SCV002617842 | uncertain significance | Cardiovascular phenotype | 2023-11-29 | criteria provided, single submitter | clinical testing | The p.R1215H variant (also known as c.3644G>A), located in coding exon 6 of the ALPK3 gene, results from a G to A substitution at nucleotide position 3644. The arginine at codon 1215 is replaced by histidine, an amino acid with highly similar properties. This variant was detected in a cardiomyopathy/arrhythmia genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Clinical Genomics Laboratory, |
RCV003883692 | SCV004697996 | uncertain significance | Cardiomyopathy, familial hypertrophic 27 | 2021-04-08 | criteria provided, single submitter | clinical testing | The p.Arg1215His variant in the ALPK3 gene has been previously reported as a heterozygous variant of uncertain significance in at least 2 unrelated individuals with cardiomyopathy (Herkert et al., 2020; van Lint et al., 2019). This variant has been identified in 9/30,554 South Asian chromosomes (40/281,284 chromosomes overall) by the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Computational tools predict that this variant does not impact protein function; however, the accuracy of in silico algorithms is limited. The Arginine at position 1215 is not evolutionarily conserved across all species, and Arg>His is observed. 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. [ACMG evidence codes used: BP4] |