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NM_000143.4(FH):c.1027C>T (p.Arg343Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 23, 2024
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:
RCV000130875.13

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]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000185779Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 23, 2024) 		germlineclinical testing

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From Ambry Genetics, SCV000185779.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The p.R343* pathogenic mutation (also known as c.1027C>T), located in coding exon 7 of the FH gene, results from a C to T substitution at nucleotide position 1027. This changes the amino acid from an arginine to a stop codon within coding exon 7. This mutation was first reported in a hereditary leiomyomatosis and renal cell carcinoma (HLRCC) kindred with cutaneous and uterine leiomyomata and type II papillary renal cell cancer (RCC) (Tomlinson IP et al. Nat Genet. 2002 Apr;30(4):406-10). This mutation has also been reported in individuals with multiple leiomyomata but no personal history of RCC (Kiuru M et al. Cancer Res. 2002 Aug;62(16):4554-7; Gardie B et al. J. Med. Genet. 2011 Apr;48(4):226-34; Venables Z et al. Clin. Exp. Dermatol. 2015 Jan;40(1):99-100). Of note, this alteration is also designated as c.898C>T and p.Arg300X in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 26, 2024