Submissions for variant NM_020778.5(ALPK3):c.1688T>G (p.Met563Arg)

dbSNP: rs150028343

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000423131	SCV000535204	uncertain significance	not provided	2024-04-16	criteria provided, single submitter	clinical testing	Reported in an individual with ARVC who also harbored a variant in the DSP gene (PMID: 38204539); In silico analysis indicates that this missense variant does not alter protein structure/function; Also known as p.(M765R); This variant is associated with the following publications: (PMID: 38204539)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000423131	SCV002199260	uncertain significance	not provided	2025-01-23	criteria provided, single submitter	clinical testing	This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 765 of the ALPK3 protein (p.Met765Arg). This variant is present in population databases (rs150028343, gnomAD 0.04%). 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: 392012). 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.
Ambry Genetics	RCV002451048	SCV002738112	likely benign	Cardiovascular phenotype	2024-04-19	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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV005404569	SCV006070214	likely benign	not specified	2025-04-09	criteria provided, single submitter	clinical testing	BP1, BP4
Clinical Genetics, Academic Medical Center	RCV000423131	SCV001925705	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000423131	SCV001976053	uncertain significance	not provided		no assertion criteria provided	clinical testing