ClinVar Miner

Submissions for variant NM_000298.6(PKLR):c.1670G>C (p.Gly557Ala)

dbSNP: rs1674489086
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001810610 SCV001474434 uncertain significance not provided 2019-08-22 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001810610 SCV002289933 likely pathogenic not provided 2022-04-09 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 557 of the PKLR protein (p.Gly557Ala). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 994383). This missense change has been observed in individual(s) with clinical features of pyruvate kinase deficiency (PMID: 10354117, 27871768). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency).

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