Submissions for variant NM_000137.4(FAH):c.577T>C (p.Cys193Arg)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV004576500	SCV005060526	likely pathogenic	Tyrosinemia type I	2024-02-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004576500	SCV005184397	likely pathogenic	Tyrosinemia type I	2024-05-01	criteria provided, single submitter	clinical testing	Variant summary: FAH c.577T>C (p.Cys193Arg) results in a non-conservative amino acid change located in the Fumarylacetoacetase-like domain, C-terminal (IPR011234) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250386 control chromosomes. c.577T>C has been reported in the literature in an individual affected with Tyrosinemia Type 1 (Ploos van Amstel_1996). At least two publications report experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Bergeron_2001, Macias_2019). The following publications have been ascertained in the context of this evaluation (PMID: 11278491, 31300554, 8557261). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV004576500	SCV005438373	pathogenic	Tyrosinemia type I	2024-12-18	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV004576500	SCV005635323	likely pathogenic	Tyrosinemia type I	2024-05-03	criteria provided, single submitter	clinical testing