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NM_000143.4(FH):c.560C>T (p.Ser187Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 28, 2017
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:
RCV000492920.11

Allele description [Variation Report for NM_000143.4(FH):c.560C>T (p.Ser187Leu)]

NM_000143.4(FH):c.560C>T (p.Ser187Leu)

Gene:
FH:fumarate hydratase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_000143.4(FH):c.560C>T (p.Ser187Leu)
HGVS:
  • NC_000001.11:g.241508781G>A
  • NG_012338.1:g.15974C>T
  • NM_000143.4:c.560C>TMANE SELECT
  • NP_000134.2:p.Ser187Leu
  • NP_000134.2:p.Ser187Leu
  • LRG_504t1:c.560C>T
  • LRG_504:g.15974C>T
  • LRG_504p1:p.Ser187Leu
  • NC_000001.10:g.241672081G>A
  • NM_000143.3:c.560C>T
  • p.[Ser187Leu]
Protein change:
S187L
Links:
dbSNP: rs398123166
NCBI 1000 Genomes Browser:
rs398123166
Molecular consequence:
  • NM_000143.4:c.560C>T - 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
SCV000581644Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Likely pathogenic
(Aug 28, 2017) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Mutations in the fumarate hydratase gene cause hereditary leiomyomatosis and renal cell cancer in families in North America.

Toro JR, Nickerson ML, Wei MH, Warren MB, Glenn GM, Turner ML, Stewart L, Duray P, Tourre O, Sharma N, Choyke P, Stratton P, Merino M, Walther MM, Linehan WM, Schmidt LS, Zbar B.

Am J Hum Genet. 2003 Jul;73(1):95-106. Epub 2003 May 22.

PubMed [citation]
PMID:
12772087
PMCID:
PMC1180594

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, SCV000581644.6

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

Description

The p.S187L variant (also known as c.560C>T), located in coding exon 5 of the FH gene, results from a C to T substitution at nucleotide position 560. The serine at codon 187 is replaced by leucine, an amino acid with dissimilar properties. This alteration was previously identified to co-segregate with disease in one family with HLRCC and was absent in 210 unaffected controls (Toro JR et al. Am. J. Hum. Genet. 2003 Jul; 73(1):95-106). Based on structural analysis, this variant is anticipated to result in a loss of fumarate binding and catalysis (Ambry internal data; Picaud S et al. J. Inherit. Metab. Dis. 2011 Jun; 34(3):671-6; Mechaly AE et al. FEBS Lett. 2012 Jun; 586(11):1606-11). Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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

Last Updated: Oct 26, 2024