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_000143.3(FH):c.738+2T>C

Help
Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Aug 20, 2021)
Last evaluated:
Sep 16, 2020
Accession:
VCV000405921.6
Variation ID:
405921
Description:
single nucleotide variant
Help

NM_000143.3(FH):c.738+2T>C

Allele ID
391136
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
1q43
Genomic location
1: 241508601 (GRCh38) GRCh38 UCSC
1: 241671901 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000001.10:g.241671901A>G
NC_000001.11:g.241508601A>G
NM_000143.3:c.738+2T>C splice donor
... more HGVS
Protein change
-
Other names
-
Canonical SPDI
NC_000001.11:241508600:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA16610056
dbSNP: rs1060500901
Varsome
Help

Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 2 criteria provided, multiple submitters, no conflicts Sep 16, 2020 RCV000458630.5
Pathogenic 1 no assertion criteria provided Jun 14, 2019 RCV001577061.1
Help
Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
FH Sufficient evidence for dosage pathogenicity No evidence available GRCh38
GRCh37
1010 1084

Submitted interpretations and evidence

Help
Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(Feb 27, 2018)
criteria provided, single submitter
Method: clinical testing
Fumarase deficiency
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000917375.1
Submitted: (Apr 24, 2019)
Evidence details
Comment:
Variant summary: FH c.738+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to … (more)
Pathogenic
(Sep 16, 2020)
criteria provided, single submitter
Method: clinical testing
Fumarase deficiency
Allele origin: germline
Invitae
Accession: SCV000544260.5
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change affects a donor splice site in intron 5 of the FH gene. It is expected to disrupt RNA splicing and likely results … (more)
Pathogenic
(Jun 14, 2019)
no assertion criteria provided
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV001804381.1
Submitted: (Aug 20, 2021)
Evidence details
Comment:
Canonical splice site variant predicted to result in an in-frame deletion of a critical region [Exon 5 with multiple PATH missense variants and the substrate … (more)

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
Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers. Muller M Clinical genetics 2017 PMID: 28300276
Novel splice site mutation in the fumarate hydratase (FH) gene is associated with multiple cutaneous leiomyomas in a Japanese patient. Yoshinaga Y The Journal of dermatology 2016 PMID: 26173633
Novel FH mutations in families with hereditary leiomyomatosis and renal cell cancer (HLRCC) and patients with isolated type 2 papillary renal cell carcinoma. Gardie B Journal of medical genetics 2011 PMID: 21398687
Splicing in action: assessing disease causing sequence changes. Baralle D Journal of medical genetics 2005 PMID: 16199547
Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer. Tomlinson IP Nature genetics 2002 PMID: 11865300

Text-mined citations for rs1060500901...

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 Aug 24, 2021