Submissions for variant NM_000161.3(GCH1):c.644T>C (p.Met215Thr)

dbSNP: rs2140038918

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV002264873	SCV002546240	likely pathogenic	GTP cyclohydrolase I deficiency with hyperphenylalaninemia		criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV002264873	SCV005044819	uncertain significance	GTP cyclohydrolase I deficiency with hyperphenylalaninemia		criteria provided, single submitter	clinical testing	The missense c.644T>C p.Met215Thr variant in GCH1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Met215Thr variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Likely Pathogenic. The amino acid change p.Met215Thr in GCH1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Met at position 215 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. Functional studies are required to prove the pathogenicity for the variant, for these reasons, this variant has been classified as Variant of Uncertain Significance VUS.