Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Johns Hopkins Genomics, |
RCV001007616 | SCV001167303 | likely pathogenic | Pyruvate kinase deficiency of red cells | 2019-11-22 | criteria provided, single submitter | clinical testing | This PKLR variant is absent from large population datasets and has not been reported in the literature, to our knowledge. Three bioinformatic tools queried predict that this substitution would be possibly damaging, and the asparagine residue at this position is evolutionarily conserved across the vertebrates assessed. This asparagine is located at the A/C subunit interface of the protein where other amino acid subsitutions have been reported in patients with hemolytic anemia due to pyruvate kinase deficiency. A different subsitution at this amino acid residue (p.Asn361Asp) has been identified in two patients with pyruvate kinase deficiency who each had a different second PKLR missense variant. We consider PKLR c.1082A>C to be likely pathogenic. |
| ARUP Laboratories, |
RCV001811621 | SCV002048272 | likely pathogenic | not provided | 2022-03-15 | criteria provided, single submitter | clinical testing | The PKLR c.1082A>C; p.Asn361Thr variant (rs1358047518), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 816680). An alternative change at this codon (p.Asn361Asp) has been reported in a compound heterozygous configuration with additional PKLR variants in one individual with PK deficiency (Lenzner 1994). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. The Asparagine at codon 361 is highly conserved, and computational analyses predict this variant is deleterious (REVEL: 0.906). Based on available information, this variant is considered to be likely pathogenic. |
| Gene |
RCV001811621 | SCV003805138 | uncertain significance | not provided | 2022-08-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Revvity Omics, |
RCV001811621 | SCV003808469 | uncertain significance | not provided | 2023-04-06 | criteria provided, single submitter | clinical testing |