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NM_000143.4(FH):c.1209del (p.Phe403fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 24, 2022
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:
RCV001010289.10

Allele description [Variation Report for NM_000143.4(FH):c.1209del (p.Phe403fs)]

NM_000143.4(FH):c.1209del (p.Phe403fs)

Gene:
FH:fumarate hydratase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_000143.4(FH):c.1209del (p.Phe403fs)
HGVS:
  • NC_000001.11:g.241502473del
  • NG_012338.1:g.22285del
  • NM_000143.4:c.1209delMANE SELECT
  • NP_000134.2:p.Phe403fs
  • LRG_504:g.22285del
  • NC_000001.10:g.241665770del
  • NC_000001.10:g.241665773del
  • NM_000143.3:c.1209delT
  • p.[Phe403Leufs*3]
Protein change:
F403fs
Links:
dbSNP: rs1060499644
NCBI 1000 Genomes Browser:
rs1060499644
Molecular consequence:
  • NM_000143.4:c.1209del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001170463Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 24, 2022) 		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

Germline Variants in Targeted Tumor Sequencing Using Matched Normal DNA.

Schrader KA, Cheng DT, Joseph V, Prasad M, Walsh M, Zehir A, Ni A, Thomas T, Benayed R, Ashraf A, Lincoln A, Arcila M, Stadler Z, Solit D, Hyman DM, Zhang L, Klimstra D, Ladanyi M, Offit K, Berger M, Robson M.

JAMA Oncol. 2016 Jan;2(1):104-11. doi: 10.1001/jamaoncol.2015.5208. Erratum in: JAMA Oncol. 2016 Feb;2(2):279. doi: 10.1001/jamaoncol.2015.6541. Hyman, David [corrected to Hyman, David M].

PubMed [citation]
PMID:
26556299
PMCID:
PMC5477989

Details of each submission

From Ambry Genetics, SCV001170463.4

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

Description

The c.1209delT pathogenic mutation, located in coding exon 8 of the FH gene, results from a deletion of one nucleotide at nucleotide position 1209, causing a translational frameshift with a predicted alternate stop codon (p.F403Lfs*3). This alteration has been previously identified in the tumor and germline of one individual with renal cell carcinoma diagnosed between age 20-29y (Schrader KA et al. JAMA Oncol, 2016 Jan;2:104-11). 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: Nov 24, 2024