ClinVar Miner

Submissions for variant NM_020778.5(ALPK3):c.4381G>C (p.Val1461Leu)

gnomAD frequency: 0.00013  dbSNP: rs143835594
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001864718 SCV002117831 uncertain significance not provided 2025-01-31 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1663 of the ALPK3 protein (p.Val1663Leu). This variant is present in population databases (rs143835594, gnomAD 0.05%). 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: 1359438). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt ALPK3 protein function with a negative predictive value of 80%. 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.
GeneDx RCV001864718 SCV003921466 uncertain significance not provided 2022-10-27 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
Ambry Genetics RCV003382659 SCV004088539 likely benign Cardiovascular phenotype 2023-07-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV005232686 SCV005878552 uncertain significance Cardiomyopathy, familial hypertrophic 27 2024-10-17 criteria provided, single submitter clinical testing The ALPK3 c.4381G>C; p.Val1461Leu variant (rs143835594), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1359438). This variant is found in the African population with an allele frequency of 0.05% (13/24,956 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is neutral (REVEL: 0.017). Due to limited information, the clinical significance of this variant is uncertain at this time.

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