NM_000137.4(FAH):c.726G>A (p.Trp242Ter) AND Tyrosinemia type I

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Jun 17, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV001004595.3

Allele description [Variation Report for NM_000137.4(FAH):c.726G>A (p.Trp242Ter)]

NM_000137.4(FAH):c.726G>A (p.Trp242Ter)

Gene:
FAH:fumarylacetoacetate hydrolase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q25.1
Genomic location:
Preferred name:
NM_000137.4(FAH):c.726G>A (p.Trp242Ter)
HGVS:
  • NC_000015.10:g.80173033G>A
  • NG_012833.1:g.25035G>A
  • NM_000137.4:c.726G>AMANE SELECT
  • NM_001374377.1:c.726G>A
  • NM_001374380.1:c.726G>A
  • NP_000128.1:p.Trp242Ter
  • NP_001361306.1:p.Trp242Ter
  • NP_001361309.1:p.Trp242Ter
  • NC_000015.9:g.80465375G>A
  • NM_000137.2:c.726G>A
Protein change:
W242*
Links:
dbSNP: rs1567118987
NCBI 1000 Genomes Browser:
rs1567118987
Molecular consequence:
  • NM_000137.4:c.726G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374377.1:c.726G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001374380.1:c.726G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Tyrosinemia type I (TYRSN1)
Synonyms:
Tyrosinemia type 1; Hepatorenal tyrosinemia; FAH deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010161; MedGen: C0268490; Orphanet: 882; OMIM: 276700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001163758Baylor Geneticscriteria provided, single submitter
Likely pathogenicgermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV001383319Invitaecriteria provided, single submitter
Pathogenic
(Jun 17, 2019)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Geographical and Ethnic Distribution of Mutations of the Fumarylacetoacetate Hydrolase Gene in Hereditary Tyrosinemia Type 1.

Angileri F, Bergeron A, Morrow G, Lettre F, Gray G, Hutchin T, Ball S, Tanguay RM.

JIMD Rep. 2015;19:43-58. doi: 10.1007/8904_2014_363. Epub 2015 Feb 15.

PubMed [citation]
PMID:
25681080
PMCID:
PMC4501228
See all PubMed Citations (5)

Details of each submission

From Baylor Genetics, SCV001163758.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001383319.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Trp242*) in the FAH gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with tyrosinemia, type 1 (PMID: 25681080). Loss-of-function variants in FAH are known to be pathogenic (PMID: 9101289, 9633815). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

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