Submissions for variant NM_002637.4(PHKA1):c.2335C>A (p.Gln779Lys)

gnomAD frequency: 0.00008  dbSNP: rs144670958

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000438434	SCV000536591	uncertain significance	not provided	2017-02-03	criteria provided, single submitter	clinical testing	The Q779K variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The NHLBI Exome Sequencing Project and the 1000 Genomes Project Consortium reports Q779K was observed in 2/6728 alleles from individuals of European background and in 1/718 alleles from individuals of South Asian background, including two hemizygous individuals. The Q779K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002522721	SCV003289877	uncertain significance	Glycogen storage disease IXd	2025-01-21	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 779 of the PHKA1 protein (p.Gln779Lys). This variant is present in population databases (rs144670958, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PHKA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 393215). 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 expected to disrupt PHKA1 protein function with a positive 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	RCV004955488	SCV005473070	uncertain significance	Inborn genetic diseases	2024-08-12	criteria provided, single submitter	clinical testing	The c.2335C>A (p.Q779K) alteration is located in exon 21 (coding exon 21) of the PHKA1 gene. This alteration results from a C to A substitution at nucleotide position 2335, causing the glutamine (Q) at amino acid position 779 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000438434	SCV001799973	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000438434	SCV001807206	uncertain significance	not provided		no assertion criteria provided	clinical testing