ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.479C>T (p.Ser160Leu)

gnomAD frequency: 0.00001  dbSNP: rs758949475
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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 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

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