Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001043118 | SCV001206833 | uncertain significance | Glycogen storage disease IXd | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 531 of the PHKA1 protein (p.Tyr531Phe). This variant is present in population databases (rs781878909, gnomAD 0.007%). 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: 840990). 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 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 | RCV003160299 | SCV003884834 | uncertain significance | Inborn genetic diseases | 2023-02-23 | criteria provided, single submitter | clinical testing | The c.1592A>T (p.Y531F) alteration is located in exon 16 (coding exon 16) of the PHKA1 gene. This alteration results from a A to T substitution at nucleotide position 1592, causing the tyrosine (Y) at amino acid position 531 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |