NM_000143.4(FH):c.1027C>T (p.Arg343Ter) AND Hereditary leiomyomatosis and renal cell cancer

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 17, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000017622.33

Allele description [Variation Report for NM_000143.4(FH):c.1027C>T (p.Arg343Ter)]

NM_000143.4(FH):c.1027C>T (p.Arg343Ter)

Gene:

FH:fumarate hydratase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_000143.4(FH):c.1027C>T (p.Arg343Ter)

Other names:

R300*; p.R343*:CGA>TGA

HGVS:

NC_000001.11:g.241504123G>A
NG_012338.1:g.20632C>T
NM_000143.4:c.1027C>TMANE SELECT
NP_000134.2:p.Arg343Ter
NP_000134.2:p.Arg343Ter
LRG_504t1:c.1027C>T
LRG_504:g.20632C>T
LRG_504p1:p.Arg343Ter
NC_000001.10:g.241667423G>A
NM_000143.3:c.1027C>T
p.R343*
p.[Arg343*]

Protein change:

R343*; ARG300TER

Links:

OMIM: 136850.0006; dbSNP: rs121913122

NCBI 1000 Genomes Browser:

rs121913122

Molecular consequence:

NM_000143.4:c.1027C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Hereditary leiomyomatosis and renal cell cancer
Synonyms:: Reed syndrome; Multiple cutaneous and uterine leiomyomatosis; Cutaneous leiomyomata with uterine leiomyomata; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007888; MedGen: C1708350; Orphanet: 523; OMIM: 150800; Human Phenotype Ontology: HP:0007437

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037897	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2002)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000537253	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	criteria provided, single submitter (DGD Variant Analysis Guidelines)	Pathogenic (Jan 17, 2017)	germline	clinical testing	DGD_Variant_Analysis_Guidelines.docx, Citation Link,
SCV003806643	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Jan 17, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000037897

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2002)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000537253

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

criteria provided, single submitter

(DGD Variant Analysis Guidelines)

Pathogenic
(Jan 17, 2017)

germline

clinical testing

DGD_Variant_Analysis_Guidelines.docx,

Citation Link,

SCV003806643

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Jan 17, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	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

Details of each submission

From OMIM, SCV000037897.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a Finnish family with the hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC; 150800), Tomlinson et al. (2002) found a nonsense mutation converting codon 300 in exon 6 of the FH gene from CGA (arg) to TGA (stop) (R300X).

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

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, SCV000537253.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

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

From Myriad Genetics, Inc., SCV003806643.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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

Last Updated: Oct 26, 2024

ClinVar

Relating variation to medicine