ClinVar Miner

Submissions for variant NM_000298.6(PKLR):c.1168G>A (p.Asp390Asn)

dbSNP: rs147034239
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001961352 SCV002256260 likely pathogenic not provided 2025-01-01 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 390 of the PKLR protein (p.Asp390Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pyruvate kinase deficiency (PMID: 9160692, 17977029, 26315463, 27871768; internal data). ClinVar contains an entry for this variant (Variation ID: 1469002). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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: 11960989, 26549847). This variant disrupts the p.Asp390 amino acid residue in PKLR. Other variant(s) that disrupt this residue have been observed in individuals with PKLR-related conditions (PMID: 31747117), which suggests that this may be a clinically significant amino acid residue. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001961352 SCV004226307 pathogenic not provided 2022-06-03 criteria provided, single submitter clinical testing PP3, PM1, PM2, PM3, PS3, PS4_moderate
Revvity Omics, Revvity RCV001961352 SCV004238109 pathogenic not provided 2023-05-19 criteria provided, single submitter clinical testing

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