ClinVar Miner

Submissions for variant NM_000298.6(PKLR):c.1516G>A (p.Val506Ile) (rs8177988)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000224042 SCV000885965 uncertain significance not provided 2018-01-22 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224042 SCV000280976 uncertain significance not provided 2015-02-06 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Fulgent Genetics,Fulgent Genetics RCV000764981 SCV000896160 uncertain significance Adenosine triphosphate, elevated, of erythrocytes; Pyruvate kinase deficiency of red cells 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000224042 SCV000617805 uncertain significance not provided 2017-10-03 criteria provided, single submitter clinical testing The V506I variant in the PKLR gene, also called PK Mallorca, has been reported previously in the heterozygous state with a second PKLR variant in a patient with PK deficiency (Pissard et al., 2006). The V506I variant was also identified in the heterozygous state in a child with concomitant hereditary spherocytosis and chronic hemolytic anemia who harbored V506I in trans with variants in hereditary spherocytosis genes; this individual's mother with V506I in the heterozygous state was asymptomatic (Zarza et al., 2000). The V506I variant is observed in 217/30782 (0.7%) alleles from individuals of South African background, including five homozygous individuals, in the ExAC dataset (Lek et al., 2016). The V506I variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret V506I as a variant of uncertain significance.

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