ClinVar Miner

Submissions for variant NM_000298.6(PKLR):c.721G>T (p.Glu241Ter) (rs201953584)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000762858 SCV000893218 pathogenic Adenosine triphosphate, elevated, of erythrocytes; Pyruvate kinase deficiency of red cells 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000295664 SCV000329970 pathogenic not provided 2016-06-28 criteria provided, single submitter clinical testing The E241X pathogenic variant in the PKLR gene has been reported previously in association with pyruvate kinase deficiency when present in the homozygous state or when in trans with another pathogenic variant (Baronciani et al., 1993; Fermo et al., 2005; Pissard et al., 2006). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The E241X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret E241X as a pathogenic variant.
Illumina Clinical Services Laboratory,Illumina 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.

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