NM_000143.4(FH):c.1052C>A (p.Ser351Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 12, 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:: RCV001782931.12

Allele description [Variation Report for NM_000143.4(FH):c.1052C>A (p.Ser351Ter)]

NM_000143.4(FH):c.1052C>A (p.Ser351Ter)

Gene:

FH:fumarate hydratase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_000143.4(FH):c.1052C>A (p.Ser351Ter)

HGVS:

NC_000001.11:g.241504098G>T
NG_012338.1:g.20657C>A
NM_000143.4:c.1052C>AMANE SELECT
NP_000134.2:p.Ser351Ter
NP_000134.2:p.Ser351Ter
LRG_504t1:c.1052C>A
LRG_504:g.20657C>A
LRG_504p1:p.Ser351Ter
NC_000001.10:g.241667398G>T
NM_000143.3:c.1052C>A

Protein change:

S351*

Links:

dbSNP: rs1060500896

NCBI 1000 Genomes Browser:

rs1060500896

Molecular consequence:

NM_000143.4:c.1052C>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000544246	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 12, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 11865300, 21398687, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000544246

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 12, 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

Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, et al.

Nat Genet. 2002 Apr;30(4):406-10. Epub 2002 Feb 25.

PubMed [citation]

PMID:: 11865300

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, Remenieras A, Kattygnarath D, Bombled J, Lefèvre S, Perrier-Trudova V, Rustin P, Barrois M, Slama A, Avril MF, Bessis D, Caron O, Caux F, Collignon P, Coupier I, Cremin C, Dollfus H, Dugast C, Escudier B, Faivre L, Field M, Gilbert-Dussardier B, et al.

J Med Genet. 2011 Apr;48(4):226-34. doi: 10.1136/jmg.2010.085068. Epub 2011 Mar 12. Erratum in: J Med Genet. 2011 Aug;48(8):576.

PubMed [citation]

PMID:: 21398687

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000544246.7

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

Description

This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in FH are known to be pathogenic (PMID: 11865300, 21398687). This variant has not been reported in the literature in individuals with FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 405912). This sequence change creates a premature translational stop signal (p.Ser351*) in the FH gene. It is expected to result in an absent or disrupted protein product.

#	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: Oct 26, 2024

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