ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1156T>C (p.Tyr386His)

dbSNP: rs199475691
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000173991 SCV000225210 uncertain significance not provided 2015-09-29 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004700531 SCV005204464 uncertain significance not specified 2024-06-11 criteria provided, single submitter clinical testing Variant summary: PAH c.1156T>C (p.Tyr386His) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251268 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1156T>C has been reported in the literature in at least one compound heterozygous individual affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria) (e.g., Rajabi_2019). These data do not allow any conclusion about variant significance. A different variant affecting the same codon has been classified as pathogenic by our lab (c.1157A>G, p.Tyr386Cys), supporting the critical relevance of codon 386 to PAH protein function. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 31623983). ClinVar contains an entry for this variant (Variation ID: 193805). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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