NM_000137.4(FAH):c.535_536del (p.Gln179fs) AND Tyrosinemia type I

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 3, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001230099.4

Allele description [Variation Report for NM_000137.4(FAH):c.535_536del (p.Gln179fs)]

NM_000137.4(FAH):c.535_536del (p.Gln179fs)

Gene:

FAH:fumarylacetoacetate hydrolase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

15q25.1

Genomic location:

Preferred name:

NM_000137.4(FAH):c.535_536del (p.Gln179fs)

HGVS:

NC_000015.10:g.80168131_80168132del
NG_012833.1:g.20133_20134del
NM_000137.4:c.535_536delMANE SELECT
NM_001374377.1:c.535_536del
NM_001374380.1:c.535_536del
NP_000128.1:p.Gln179fs
NP_001361306.1:p.Gln179fs
NP_001361309.1:p.Gln179fs
NC_000015.9:g.80460472_80460473del
NC_000015.9:g.80460473_80460474del
NM_000137.2:c.535_536del

Protein change:

Q179fs

Links:

dbSNP: rs2041210282

NCBI 1000 Genomes Browser:

rs2041210282

Molecular consequence:

NM_000137.4:c.535_536del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374377.1:c.535_536del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001374380.1:c.535_536del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Mus musculus neuregulin 3 (Nrg3), transcript variant 1, mRNA
Mus musculus neuregulin 3 (Nrg3), transcript variant 1, mRNA
gi|298231175|ref|NM_008734.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001402569	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 3, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9101289, 9633815, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001402569

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 3, 2019)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the fumarylacetoacetate hydrolase gene causing hereditary tyrosinemia type I: overview.

St-Louis M, Tanguay RM.

Hum Mutat. 1997;9(4):291-9. Review.

PubMed [citation]

PMID:: 9101289

Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries.

Bergman AJ, van den Berg IE, Brink W, Poll-The BT, Ploos van Amstel JK, Berger R.

Hum Mutat. 1998;12(1):19-26.

PubMed [citation]

PMID:: 9633815

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001402569.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln179Aspfs*4) 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 not been reported in the literature in individuals with FAH-related conditions. Loss-of-function variants in FAH are known to be pathogenic (PMID: 9101289, 9633815). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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