NM_000143.4(FH):c.737del (p.Gln246fs) AND Fumarase deficiency

delete

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 2, 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:: RCV001058354.3

Allele description

NM_000143.4(FH):c.737del (p.Gln246fs)

Gene:

FH:fumarate hydratase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_000143.4(FH):c.737del (p.Gln246fs)

HGVS:

NC_000001.11:g.241508604del
NG_012338.1:g.16151del
NM_000143.4:c.737delMANE SELECT
NP_000134.2:p.Gln246fs
NP_000134.2:p.Gln246fs
LRG_504t1:c.737del
LRG_504:g.16151del
LRG_504p1:p.Gln246fs
NC_000001.10:g.241671904del
NM_000143.3:c.737del

Protein change:

Q246fs

Links:

dbSNP: rs727503928

NCBI 1000 Genomes Browser:

rs727503928

Molecular consequence:

NM_000143.4:c.737del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Fumarase deficiency (FMRD)
Synonyms:: Fumaric aciduria; Fumarate Hydratase Deficiency
Identifiers:: MONDO: MONDO:0011730; MedGen: C0342770; Orphanet: 24; OMIM: 606812

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001222914	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 2, 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

SCV001222914

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 2, 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 Invitae, SCV001222914.3

#	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.Gln246Argfs*10) in the FH 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 FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 167067). Loss-of-function variants in FH are known to be pathogenic (PMID: 11865300, 21398687). 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: Dec 24, 2022

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