Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000295664 | SCV000329970 | pathogenic | not provided | 2025-01-30 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 8483951, 15953013, 17574881, 26046366, 9160692, 11328279, 28133914, 26459649, 19758413, 24762414, 7948315, 29519373, 32761227, 31589614, 16704447, 27354418, 7706479) |
| Illumina Laboratory Services, |
RCV000261579 | SCV000348603 | pathogenic | Pyruvate kinase deficiency of red cells | 2017-04-27 | criteria provided, single submitter | clinical testing | The PKLR c.721G>T (p.Glu241Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. The p.Glu241Ter variant has been reported in five studies in which it has been identified in a total of 15 individuals with pyruvate kinase deficiency, including in one in a homozygous state, in 12 in a compound heterozygous state, and in two in a heterozygous state in whom a second variant was not identified (Lakomek et al. 1994; Baronciani et al. 1995; Zarza et al. 1998; Pissard et al. 2006; Percy et al. 2007). Control data are unavailable for this variant, which is reported at a frequency of 0.00005 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the collective evidence, the p.Glu241Ter variant is classified as pathogenic for pyruvate kinase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Fulgent Genetics, |
RCV000762858 | SCV000893218 | pathogenic | Pyruvate kinase hyperactivity; Pyruvate kinase deficiency of red cells | 2022-04-21 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000295664 | SCV001474140 | pathogenic | not provided | 2022-04-07 | criteria provided, single submitter | clinical testing | The PKLR c.721G>T; p.Glu241Ter variant (rs201953584) is reported in the literature in at least 11 individuals affected with PK deficiency (Baronciani 1993, Baronciani 1995, Christensen 2016, Lakomek 1994, Percy 2007, Pissard 2006, Svidnicki 2018, Zarza 1998). This variant is also reported in ClinVar (Variation ID: 280113). This variant is found in the non-Finnish European population with an allele frequency of 0.009% (12/126,486 alleles) in the Genome Aggregation Database. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. |
| Mayo Clinic Laboratories, |
RCV000295664 | SCV001715318 | pathogenic | not provided | 2019-06-20 | criteria provided, single submitter | clinical testing | PVS1, PS4_moderate, PM3, PP4, PP5 |
| Revvity Omics, |
RCV000295664 | SCV002018837 | pathogenic | not provided | 2023-06-15 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000295664 | SCV002240687 | pathogenic | not provided | 2023-05-06 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 280113). This premature translational stop signal has been observed in individual(s) with pyruvate kinase deficiency (PMID: 8483951, 27354418). This variant is present in population databases (rs201953584, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Glu241*) in the PKLR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKLR are known to be pathogenic (PMID: 15953013, 26832193). |