Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation

ClinVar Genomic variation as it relates to human health

Advanced search

NM_000137.4(FAH):c.1A>G (p.Met1Val)

Help
Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
5 (Most recent: Sep 30, 2021)
Last evaluated:
Sep 21, 2020
Accession:
VCV000372766.8
Variation ID:
372766
Description:
single nucleotide variant
Help

NM_000137.4(FAH):c.1A>G (p.Met1Val)

Allele ID
360304
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
15q25.1
Genomic location
15: 80153055 (GRCh38) GRCh38 UCSC
15: 80445397 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000015.10:g.80153055A>G
NG_012833.1:g.5057A>G
NM_000137.4:c.1A>G MANE Select NP_000128.1:p.Met1Val missense
... more HGVS
Protein change
M1V
Other names
-
Canonical SPDI
NC_000015.10:80153054:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA16043027
dbSNP: rs1057517972
VarSome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 4 criteria provided, multiple submitters, no conflicts Sep 21, 2020 RCV000984171.5
Pathogenic 1 criteria provided, single submitter Sep 16, 2019 RCV000414667.2
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
FAH - - GRCh38
GRCh37
396 415

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Sep 16, 2019)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000491239.3
Submitted: (Sep 30, 2021)
Evidence details
Comment:
Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts … (more)
Pathogenic
(Sep 21, 2020)
criteria provided, single submitter
Method: clinical testing
Tyrosinemia type I
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001437349.1
Submitted: (Oct 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: FAH c.1A>G (p.Met1Val) alters the initiation codon and is predicted to result either in absence of the protein or truncation of the encoded … (more)
Pathogenic
(Aug 20, 2020)
criteria provided, single submitter
Method: clinical testing
Tyrosinemia type I
Allele origin: germline
Invitae
Accession: SCV001227505.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (3)
Comment:
This sequence change affects the initiator methionine of the FAH mRNA. The next in-frame methionine is located at codon 71. This variant is not present … (more)
Likely pathogenic
(Feb 06, 2014)
no assertion criteria provided
Method: clinical testing
Tyrosinemia type I
Allele origin: unknown
Counsyl
Accession: SCV001132185.1
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (3)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Tyrosinemia type I
Allele origin: germline
Natera, Inc.
Accession: SCV001461573.1
Submitted: (Dec 28, 2020)
Evidence details

Functional evidence

Help
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

Help
Title Author Journal Year Link
Mutational spectrum of Mexican patients with tyrosinemia type 1: In silico modeling and predicted pathogenic effect of a novel missense FAH variant. Ibarra-González I Molecular genetics & genomic medicine 2019 PMID: 31568711
Hereditary tyrosinemia type I-associated mutations in fumarylacetoacetate hydrolase reduce the enzyme stability and increase its aggregation rate. Macias I The Journal of biological chemistry 2019 PMID: 31300554
Tyrosinemia type 1: a rare and forgotten cause of reversible hypertrophic cardiomyopathy in infancy. Mohamed S BMC research notes 2013 PMID: 24016420
Identification of mutations causing hereditary tyrosinemia type I in patients of Middle Eastern origin. Imtiaz F Molecular genetics and metabolism 2011 PMID: 21764616
Persistent coagulopathy during Escherichia coli sepsis in a previously healthy infant revealed undiagnosed tyrosinaemia type 1. Georgouli H BMJ case reports 2010 PMID: 22802474
Gene symbol: FAH. Disease: tyrosinaemia 1. Arranz A Human genetics 2005 PMID: 16521249

Text-mined citations for rs1057517972...

Help
These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 27, 2021