Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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. |