ClinVar Miner

Submissions for variant NM_000317.3(PTS):c.370G>T (p.Val124Leu) (rs150726932)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672207 SCV000797288 uncertain significance BH4-deficient hyperphenylalaninemia A 2018-01-19 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000672207 SCV000915500 uncertain significance BH4-deficient hyperphenylalaninemia A 2018-09-14 criteria provided, single submitter clinical testing The PTS c.370G>T (p.Val124Leu)missense variant has been reported in a single study in which it is found in a compound heterozygous state with a second missense variant in one individual with a mild presentation of 6-pyruvoyltetrahydropterin synthase deficiency (Dudesek et al. 2000). Control data are unavailable for this variant, which is reported at a frequency of 0.0001454 in the Latino population of the Genome Aggregation Database. Functional studies revealed that p.Val124Leu recombinant protein had no detectable PTPS enzyme activity in COS-1 cells. Based on the limited evidence, the p.Phe56Ile variant is classified as a variant of unknown significance but suspicious for pathogenicity for 6-pyruvoyltetrahydropterin synthase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000672207 SCV000934117 likely pathogenic BH4-deficient hyperphenylalaninemia A 2020-10-18 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 124 of the PTS protein (p.Val124Leu). The valine residue is moderately conserved and there is a small physicochemical difference between valine and leucine. This variant has been observed in individual(s) with PTPS deficiency (PMID: 11388593, 27243974). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 556231). This variant has been reported to affect PTS protein function (PMID: 11388593). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Baylor Genetics RCV000672207 SCV001163279 likely pathogenic BH4-deficient hyperphenylalaninemia A criteria provided, single submitter clinical testing
Nilou-Genome Lab RCV000672207 SCV001712372 uncertain significance BH4-deficient hyperphenylalaninemia A 2021-05-18 criteria provided, single submitter clinical testing

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