ClinVar Miner

Submissions for variant NM_000298.6(PKLR):c.1151C>T (p.Thr384Met)

gnomAD frequency: 0.00001  dbSNP: rs74315362
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005089142 SCV005833934 pathogenic not provided 2024-06-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 384 of the PKLR protein (p.Thr384Met). This variant is present in population databases (rs74315362, gnomAD 0.006%). This missense change has been observed in individual(s) with hemolytic anemia (PMID: 1896471, 7948315). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1507). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKLR protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PKLR function (PMID: 1896471, 11960989). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000001572 SCV000021727 pathogenic Pyruvate kinase deficiency of red cells 1991-09-15 no assertion criteria provided literature only

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