ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.501+4A>T

gnomAD frequency: 0.00009  dbSNP: rs375169579
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199215 SCV000252398 pathogenic not provided 2023-06-09 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss-of-function (Mayr JA et al., 2011); This variant is associated with the following publications: (PMID: 31288420, 34426522, 31589614, 36175994, 31440721, 33086386, 33231275, 22152682)
Institute Of Human Genetics Munich, Klinikum Rechts Der Isar, Tu München RCV000578364 SCV000680413 pathogenic Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2017-11-28 criteria provided, single submitter clinical testing
Invitae RCV000578364 SCV000960745 pathogenic Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2023-12-06 criteria provided, single submitter clinical testing This sequence change falls in intron 7 of the TPK1 gene. It does not directly change the encoded amino acid sequence of the TPK1 protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs375169579, gnomAD 0.02%). This variant has been observed in individual(s) with thiamine pyrophosphokinase deficiency (PMID: 22152682). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 215275). Studies have shown that this variant alters TPK1 gene expression (PMID: 22152682). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 7, but is expected to preserve the integrity of the reading-frame (PMID: 22152682). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000578364 SCV001520668 pathogenic Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2020-08-12 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Fulgent Genetics, Fulgent Genetics RCV000578364 SCV002804793 pathogenic Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2021-08-12 criteria provided, single submitter clinical testing
OMIM RCV000578364 SCV000044823 pathogenic Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2011-12-09 no assertion criteria provided literature only

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