Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002512653 | SCV003523246 | uncertain significance | not provided | 2022-03-18 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Arg163 amino acid residue in PKLR. Other variant(s) that disrupt this residue have been observed in individuals with PKLR-related conditions (PMID: 2018831, 19085939), which suggests that this may be a clinically significant amino acid residue. Experimental studies have shown that this missense change affects PKLR function (PMID: 2018831). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1506). This variant is also known as PK Linz variant, a C to T base exchange at position 394 . This missense change has been observed in individual(s) with pyruvate kinase deficiency (PMID: 2018831; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 163 of the PKLR protein (p.Arg163Cys). |
OMIM | RCV000001571 | SCV000021726 | pathogenic | Pyruvate kinase deficiency of red cells | 1991-05-01 | no assertion criteria provided | literature only |