NM_000143.4(FH):c.553_554insTG (p.Gln185fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 20, 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:: RCV000572356.11

Allele description [Variation Report for NM_000143.4(FH):c.553_554insTG (p.Gln185fs)]

NM_000143.4(FH):c.553_554insTG (p.Gln185fs)

Gene:

FH:fumarate hydratase [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_000143.4(FH):c.553_554insTG (p.Gln185fs)

HGVS:

NC_000001.11:g.241511968_241511969insCA
NG_012338.1:g.12786_12787insTG
NM_000143.4:c.553_554insTGMANE SELECT
NP_000134.2:p.Gln185fs
NP_000134.2:p.Gln185fs
LRG_504t1:c.553_554insTG
LRG_504:g.12786_12787insTG
LRG_504p1:p.Gln185fs
NC_000001.10:g.241675268_241675269insCA
NM_000143.3:c.553_554insTG
p.[Gln185Leufs*18]

Protein change:

Q185fs

Links:

dbSNP: rs768182640

NCBI 1000 Genomes Browser:

rs768182640

Molecular consequence:

NM_000143.4:c.553_554insTG - 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

Recent activity

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weak chloroplast movement under blue light protein (DUF827) [Arabidopsis thalian...
weak chloroplast movement under blue light protein (DUF827) [Arabidopsis thaliana]
gi|15221217|ref|NP_172679.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000664627	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jan 20, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000664627

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jan 20, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Use of Whole Genome Sequencing for Diagnosis and Discovery in the Cancer Genetics Clinic.

Foley SB, Rios JJ, Mgbemena VE, Robinson LS, Hampel HL, Toland AE, Durham L, Ross TS.

EBioMedicine. 2015 Jan;2(1):74-81.

PubMed [citation]

PMID:: 26023681
PMCID:: PMC4444225

Details of each submission

From Ambry Genetics, SCV000664627.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The c.553_554insTG pathogenic mutation, located in coding exon 4 of the FH gene, results from an insertion of two nucleotides at position 553, causing a translational frameshift with a predicted alternate stop codon (p.Q185Lfs*18). This mutation was reported in a 33-year-old female diagnosed with leiomyoma who also carried a RAD51C mutation, and had a family history of breast cancer, colon cancer, renal cell carcinoma, and leiomyoma (Foley SB et al. EBioMedicine 2015 Jan; 2(1):74-81). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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