ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.136G>A (p.Asp46Asn)

gnomAD frequency: 0.00002  dbSNP: rs551699564
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001890628 SCV002156921 uncertain significance Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2021-12-31 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 46 of the TPK1 protein (p.Asp46Asn). This variant is present in population databases (rs551699564, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TPK1-related conditions. 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 C15"). 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.
Ambry Genetics RCV002553452 SCV003574639 uncertain significance Inborn genetic diseases 2021-08-13 criteria provided, single submitter clinical testing The c.136G>A (p.D46N) alteration is located in exon 4 (coding exon 3) of the TPK1 gene. This alteration results from a G to A substitution at nucleotide position 136, causing the aspartic acid (D) at amino acid position 46 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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