NM_000143.4(FH):c.1016C>A (p.Ala339Glu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Mar 10, 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:: RCV002339570.9

Allele description [Variation Report for NM_000143.4(FH):c.1016C>A (p.Ala339Glu)]

NM_000143.4(FH):c.1016C>A (p.Ala339Glu)

Gene:

FH:fumarate hydratase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_000143.4(FH):c.1016C>A (p.Ala339Glu)

HGVS:

NC_000001.11:g.241504134G>T
NG_012338.1:g.20621C>A
NM_000143.4:c.1016C>AMANE SELECT
NP_000134.2:p.Ala339Glu
LRG_504t1:c.1016C>A
LRG_504:g.20621C>A
NC_000001.10:g.241667434G>T
NM_000143.3:c.1016C>A

Protein change:

A339E

Links:

dbSNP: rs1659852423

NCBI 1000 Genomes Browser:

rs1659852423

Molecular consequence:

NM_000143.4:c.1016C>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002643532	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 10, 2017)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002643532

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 10, 2017)

germline

clinical testing

Citation Link

Help

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

Details of each submission

From Ambry Genetics, SCV002643532.2

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

Description

The p.A339E variant (also known as c.1016C>A), located in coding exon 7 of the FH gene, results from a C to A substitution at nucleotide position 1016. The alanine at codon 339 is replaced by glutamic acid, an amino acid with dissimilar properties. This variant has been observed in at least one individual who meets clinical diagnostic criteria for Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Internal structural analysis indicates that substitution is predicted to be more destabilizing than other nearby, known pathogenic variants (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic.

#	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: Oct 26, 2024

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