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NM_000143.4(FH):c.698G>A (p.Arg233His) AND Spinocerebellar ataxia 45

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 13, 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:
RCV004541007.1

Allele description [Variation Report for NM_000143.4(FH):c.698G>A (p.Arg233His)]

NM_000143.4(FH):c.698G>A (p.Arg233His)

Gene:
FH:fumarate hydratase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_000143.4(FH):c.698G>A (p.Arg233His)
Other names:
R190H; p.R233H:CGT>CAT
HGVS:
  • NC_000001.11:g.241508643C>T
  • NG_012338.1:g.16112G>A
  • NM_000143.4:c.698G>AMANE SELECT
  • NP_000134.2:p.Arg233His
  • NP_000134.2:p.Arg233His
  • LRG_504t1:c.698G>A
  • LRG_504:g.16112G>A
  • LRG_504p1:p.Arg233His
  • NC_000001.10:g.241671943C>T
  • NM_000143.3:c.698G>A
  • P07954:p.Arg233His
  • p.[Arg233His]
Protein change:
R233H; ARG190HIS
Links:
UniProtKB: P07954#VAR_013501; OMIM: 136850.0007; dbSNP: rs121913123
NCBI 1000 Genomes Browser:
rs121913123
Molecular consequence:
  • NM_000143.4:c.698G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Spinocerebellar ataxia 45
Identifiers:
MONDO: MONDO:0033480; MedGen: C4540400; OMIM: 617769

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005040788Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Mar 13, 2024) 		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

Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.

Tomlinson IP, Alam NA, Rowan AJ, Barclay E, Jaeger EE, Kelsell D, Leigh I, Gorman P, Lamlum H, Rahman S, Roylance RR, Olpin S, Bevan S, Barker K, Hearle N, Houlston RS, Kiuru M, Lehtonen R, Karhu A, Vilkki S, Laiho P, Eklund C, et al.

Nat Genet. 2002 Apr;30(4):406-10. Epub 2002 Feb 25.

PubMed [citation]
PMID:
11865300

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
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005040788.1

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

Description

Variant summary: FAT2 c.698G>A (p.Gly233Asp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7.2e-05 in 250934 control chromosomes (gnomAD). To our knowledge, no occurrence of c.698G>A in individuals affected with Spinocerebellar Ataxia 45 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Oct 26, 2024