Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mayo Clinic Laboratories, |
RCV001508881 | SCV001715312 | pathogenic | not provided | 2020-11-19 | criteria provided, single submitter | clinical testing | PS4, PP3, PM1, PM3, PP4 |
| Revvity Omics, |
RCV001508881 | SCV003808474 | uncertain significance | not provided | 2024-01-10 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001508881 | SCV005834266 | uncertain significance | not provided | 2024-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 392 of the PKLR protein (p.Ala392Thr). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with hemolytic anemia (PMID: 8180378, 26728349). ClinVar contains an entry for this variant (Variation ID: 1163641). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PKLR 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. |
| Prevention |
RCV003948488 | SCV004766453 | likely pathogenic | PKLR-related disorder | 2023-12-06 | no assertion criteria provided | clinical testing | The PKLR c.1174G>A variant is predicted to result in the amino acid substitution p.Ala392Thr. This variant was reported in the compound heterozygous state in individuals with pyruvate kinase deficiency and hemolytic anemia (Kager et al. 2016. PubMed ID: 26728349; Kazi et al. 2022. J Hematol Allied Sci 2022;2:99-100, https://jhas-bsh.com/pyruvate-kinase-deficiency-a-rare-cause-of-hemolytic-anemia-a-case-report-from-north-eastern-india/). This variant has also been documented in the heterozygous state in an individual with a milder phenotype (patient #11, Lenzner et al. 1994. PubMed ID: 8180378) and in an individual with reduced pyruvate kinase activity (Yavarian et al. 2007. PubMed ID: 17977029). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as likely pathogenic. |