ClinVar Miner

Submissions for variant NM_002637.4(PHKA1):c.1727C>A (p.Thr576Lys)

gnomAD frequency: 0.00009  dbSNP: rs1474761630
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000616923 SCV000725411 likely benign not specified 2017-12-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV001350766 SCV001545184 uncertain significance Glycogen storage disease IXd 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 576 of the PHKA1 protein (p.Thr576Lys). This variant is present in population databases (no rsID available, gnomAD 0.008%). 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: 513874). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PHKA1 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 RCV004024968 SCV005002737 uncertain significance Inborn genetic diseases 2023-11-03 criteria provided, single submitter clinical testing The c.1727C>A (p.T576K) alteration is located in exon 17 (coding exon 17) of the PHKA1 gene. This alteration results from a C to A substitution at nucleotide position 1727, causing the threonine (T) at amino acid position 576 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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