ClinVar Miner

Submissions for variant NM_000317.3(PTS):c.1A>G (p.Met1Val)

dbSNP: rs2135407146
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001378592 SCV001576194 pathogenic 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency 2023-09-20 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the PTS mRNA. The next in-frame methionine is located at codon 69. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with tetrahydrobiopterin-deficient hyperphenylalaninemia (PMID: 22237589, 29499199, 30926181). ClinVar contains an entry for this variant (Variation ID: 1067348). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the PTS protein in which other variant(s) (p.Thr67Met) have been determined to be pathogenic (PMID: 11438997, 11694255, 16850690, 22237589). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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