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NM_000143.4(FH):c.478A>G (p.Arg160Gly) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 16, 2023
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:
RCV001023046.10

Allele description [Variation Report for NM_000143.4(FH):c.478A>G (p.Arg160Gly)]

NM_000143.4(FH):c.478A>G (p.Arg160Gly)

Gene:
FH:fumarate hydratase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_000143.4(FH):c.478A>G (p.Arg160Gly)
HGVS:
  • NC_000001.11:g.241512044T>C
  • NG_012338.1:g.12711A>G
  • NM_000143.4:c.478A>GMANE SELECT
  • NP_000134.2:p.Arg160Gly
  • NP_000134.2:p.Arg160Gly
  • LRG_504t1:c.478A>G
  • LRG_504:g.12711A>G
  • LRG_504p1:p.Arg160Gly
  • NC_000001.10:g.241675344T>C
  • NM_000143.3:c.478A>G
Protein change:
R160G
Links:
dbSNP: rs878853694
NCBI 1000 Genomes Browser:
rs878853694
Molecular consequence:
  • NM_000143.4:c.478A>G - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001184862Ambry Genetics
criteria provided, single submitter

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

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.

Wei MH, Toure O, Glenn GM, Pithukpakorn M, Neckers L, Stolle C, Choyke P, Grubb R, Middelton L, Turner ML, Walther MM, Merino MJ, Zbar B, Linehan WM, Toro JR.

J Med Genet. 2006 Jan;43(1):18-27. Epub 2005 Jun 3.

PubMed [citation]
PMID:
15937070
PMCID:
PMC2564499

Structural basis of fumarate hydratase deficiency.

Picaud S, Kavanagh KL, Yue WW, Lee WH, Muller-Knapp S, Gileadi O, Sacchettini J, Oppermann U.

J Inherit Metab Dis. 2011 Jun;34(3):671-6. doi: 10.1007/s10545-011-9294-8. Epub 2011 Mar 29.

PubMed [citation]
PMID:
21445611
PMCID:
PMC3109261
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV001184862.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

The p.R160G pathogenic mutation (also known as c.478A>G), located in coding exon 4 of the FH gene, results from an A to G substitution at nucleotide position 478. The arginine at codon 160 is replaced by glycine, an amino acid with dissimilar properties. This alteration, sometimes designated as c.349A>G in the literature, has been identified in individuals with a personal and/or family history that is consistent with FH-related disease (Ambry internal data; Wei MH et al. J. Med. Genet., 2006 Jan;43:18-27; Picaud S et al. J. Inherit. Metab. Dis., 2011 Jun;34:671-6; Scharnitz T, et al. Am J Cancer Res 2023 Jan;13(1):236-244). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Aug 25, 2024