ClinVar Miner

Submissions for variant NM_000317.3(PTS):c.84-3C>G (rs1230781262)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000668809 SCV000793473 likely pathogenic BH4-deficient hyperphenylalaninemia A 2017-08-22 criteria provided, single submitter clinical testing
Invitae RCV000668809 SCV000814118 pathogenic BH4-deficient hyperphenylalaninemia A 2020-09-19 criteria provided, single submitter clinical testing This sequence change falls in intron 1 of the PTS gene. It does not directly change the encoded amino acid sequence of the PTS protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in combination with another PTS variant in individuals affected with biopterin deficient hyperphenylalaninemia (PMID: 9222757, 27246466) and in one of these individuals, the variant has been observed on the opposite chromosome (in trans) from another pathogenic variant. This latter finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. This variant is also known as delK29-S32 in the literature. Experimental studies have shown that this intronic change abrogates PTS enzyme activity in vitro (PMID: 9222757). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091030 SCV001246862 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001091030 SCV001446717 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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