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NM_000143.4(FH):c.556A>T (p.Ser186Cys) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 20, 2014
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:
RCV000494364.3

Allele description [Variation Report for NM_000143.4(FH):c.556A>T (p.Ser186Cys)]

NM_000143.4(FH):c.556A>T (p.Ser186Cys)

Gene:
FH:fumarate hydratase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_000143.4(FH):c.556A>T (p.Ser186Cys)
HGVS:
  • NC_000001.11:g.241508785T>A
  • NG_012338.1:g.15970A>T
  • NM_000143.4:c.556A>TMANE SELECT
  • NP_000134.2:p.Ser186Cys
  • NP_000134.2:p.Ser186Cys
  • LRG_504t1:c.556A>T
  • LRG_504:g.15970A>T
  • LRG_504p1:p.Ser186Cys
  • NC_000001.10:g.241672085T>A
  • NM_000143.3:c.556A>T
Protein change:
S186C
Links:
dbSNP: rs1131691233
NCBI 1000 Genomes Browser:
rs1131691233
Molecular consequence:
  • NM_000143.4:c.556A>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

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000581629Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jun 20, 2014) 		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, SCV000581629.6

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

Description

The p.D189V variant (also known as c.556A>T) located in coding exon 5 of the FH gene. The aspartic acid at codon 189 is replaced by valine, an amino acid with highly dissimilar properties. This change occurs in the first base pair of exon 5 which makes it likely to have some effect on normal mRNA splicing. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.31% (greater than 300 alleles tested) in our clinical cohort (includes this individual). Based on protein sequence alignment, this amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be probably damaging and deleterious by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.D189V remains unclear.

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

Last Updated: May 1, 2024