Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000627286 | SCV000748278 | likely pathogenic | not provided | 2018-03-13 | criteria provided, single submitter | clinical testing | The R672X nonsense variant in the PHKB gene has previously been identified as heterozygous in an individual with Hirschsprung disease; a second variant in PHKB was not identified (Zhang et al., 2017). The R672X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. In summary, we interpret R672X to be a likely pathogenic variant. |
3billion | RCV002250673 | SCV002521748 | pathogenic | Glycogen storage disease IXb | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.001%). Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with PHKB- related disorder (ClinVar ID: VCV000523816). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
Invitae | RCV002250673 | SCV003443515 | pathogenic | Glycogen storage disease IXb | 2023-08-30 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg672*) in the PHKB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHKB are known to be pathogenic (PMID: 9215682, 9326319). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with PHKB-related conditions. ClinVar contains an entry for this variant (Variation ID: 523816). For these reasons, this variant has been classified as Pathogenic. |
Center for Genomic Medicine, |
RCV002250673 | SCV004805411 | uncertain significance | Glycogen storage disease IXb | 2024-03-25 | criteria provided, single submitter | research |