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NM_000143.4(FH):c.395_399del (p.Lys131_Leu132insTer) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 16, 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:
RCV004020397.1

Allele description [Variation Report for NM_000143.4(FH):c.395_399del (p.Lys131_Leu132insTer)]

NM_000143.4(FH):c.395_399del (p.Lys131_Leu132insTer)

Gene:
FH:fumarate hydratase [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_000143.4(FH):c.395_399del (p.Lys131_Leu132insTer)
HGVS:
  • NC_000001.11:g.241512123ATTTA[1]
  • NG_012338.1:g.12623TAAAT[1]
  • NM_000143.4:c.395_399delMANE SELECT
  • NP_000134.2:p.Lys131_Leu132insTer
  • LRG_504t1:c.395_399del
  • LRG_504:g.12623TAAAT[1]
  • NC_000001.10:g.241675423ATTTA[1]
  • NC_000001.10:g.241675423_241675427del
  • NM_000143.3:c.395_399del
  • NM_000143.3:c.395_399delTAAAT
  • p.L132*
  • p.[Leu132*]
Links:
dbSNP: rs863223995
NCBI 1000 Genomes Browser:
rs863223995
Molecular consequence:
  • NM_000143.4:c.395_399del - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005032736Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 16, 2024) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Reassessing the clinical spectrum associated with hereditary leiomyomatosis and renal cell carcinoma syndrome in French FH mutation carriers.

Muller M, Ferlicot S, Guillaud-Bataille M, Le Teuff G, Genestie C, Deveaux S, Slama A, Poulalhon N, Escudier B, Albiges L, Soufir N, Avril MF, Gardie B, Saldana C, Allory Y, Gimenez-Roqueplo AP, Bressac-de Paillerets B, Richard S, Benusiglio PR.

Clin Genet. 2017 Dec;92(6):606-615. doi: 10.1111/cge.13014. Epub 2017 May 2. Erratum in: Clin Genet. 2018 May;93(5):1118. doi: 10.1111/cge.13222.

PubMed [citation]
PMID:
28300276

Details of each submission

From Ambry Genetics, SCV005032736.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The c.395_399delTAAAT pathogenic mutation, located in coding exon 4 of the FH gene, results from a deletion of 5 nucleotides at nucleotide positions 395 to 399, causing a translational frameshift with a predicted alternate stop codon (p.L132*). This variant has been identified in a French HLRCC cohort (Muller M et al. Clin Genet, 2017 Dec;92:606-615). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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: Jun 2, 2024