Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001066752 | SCV001231770 | uncertain significance | Childhood encephalopathy due to thiamine pyrophosphokinase deficiency | 2021-09-02 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 160 of the TPK1 protein (p.Ser160Leu). The serine residue is moderately conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs758949475, ExAC 0.01%). This missense change has been observed in individual(s) with clinical features of thiamine metabolism dysfunction syndrome (PMID: 25458521). 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"). Experimental studies have shown that this missense change affects TPK1 function (PMID: 25458521, 30483896). 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. |
OMIM | RCV001066752 | SCV002547470 | pathogenic | Childhood encephalopathy due to thiamine pyrophosphokinase deficiency | 2022-07-13 | no assertion criteria provided | literature only |