Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001883690 | SCV002145741 | uncertain significance | not provided | 2024-11-27 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the ALPK3 mRNA. It is expected to extend the length of the ALPK3 protein by 49 additional amino acid residues. This variant is present in population databases (rs753251432, gnomAD 0.002%). 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: 1379292). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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 | RCV002343957 | SCV002647632 | uncertain significance | Cardiovascular phenotype | 2021-11-17 | criteria provided, single submitter | clinical testing | The c.5721delG variant, located in coding exon 14 of the ALPK3 gene, results from a deletion of one nucleotide at nucleotide position 5721, causing a translational frameshift with a predicted alternate stop codon (p.*1908Sext*49). This alteration disrupts the stop codon of the ALPK3 gene and is predicted to preserve the native sequence while resulting in the elongation of the protein by 49 amino acids. The exact functional effect of the additional amino acids is unknown. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV002471176 | SCV002769018 | uncertain significance | Cardiomyopathy, familial hypertrophic 27 | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with familial hypertrophic cardiomyopathy 27 (MIM#618052). (I) 0106 - This gene is associated with autosomal recessive disease. (I) 0208 - Variant is predicted to result in an elongated protein. (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD (v2) <0.01 for a recessive condition (3 heterozygotes, 0 homozygotes). (SP) 0705 - No comparable elongated variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been reported once as VUS in LOVD. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |