ClinVar Miner

Submissions for variant NM_000137.4(FAH):c.456G>A (p.Trp152Ter)

dbSNP: rs370686447
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000627249 SCV000231477 pathogenic not provided 2013-06-26 criteria provided, single submitter clinical testing
GeneDx RCV000627249 SCV000748240 pathogenic not provided 2018-03-22 criteria provided, single submitter clinical testing The W152X variant in the FAH gene has been reported previously in the compound heterozygous state in an individual with persistent diarrhea, hepatomegaly, ascites, elevated serum alpha-fetoprotein and tyrosine levels and elevated succinylacetone in urine. This was consistent with a diagnosis of tyrosinemia type 1 in this patient, his sister was also previously diagnosed with tyrosinemia type 1 (Dou et al., 2013). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W152X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret W152X as a pathogenic variant.
Counsyl RCV000179256 SCV000794531 likely pathogenic Tyrosinemia type I 2017-09-28 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000179256 SCV000893380 pathogenic Tyrosinemia type I 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000179256 SCV002237125 pathogenic Tyrosinemia type I 2024-01-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp152*) in the FAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAH are known to be pathogenic (PMID: 9101289, 9633815). This variant is present in population databases (rs370686447, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with FAH-related conditions. ClinVar contains an entry for this variant (Variation ID: 92445). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000179256 SCV004195889 pathogenic Tyrosinemia type I 2023-07-31 criteria provided, single submitter clinical testing

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