NM_000143.4(FH):c.1015_1024delinsT (p.Ala339_Ile342delinsPhe) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 5, 2021
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:: RCV003865865.2

Allele description [Variation Report for NM_000143.4(FH):c.1015_1024delinsT (p.Ala339_Ile342delinsPhe)]

NM_000143.4(FH):c.1015_1024delinsT (p.Ala339_Ile342delinsPhe)

Gene:

FH:fumarate hydratase [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_000143.4(FH):c.1015_1024delinsT (p.Ala339_Ile342delinsPhe)

HGVS:

NC_000001.11:g.241504126_241504135delinsA
NG_012338.1:g.20620_20629delinsT
NM_000143.4:c.1015_1024delinsTMANE SELECT
NP_000134.2:p.Ala339_Ile342delinsPhe
NP_000134.2:p.Ala339_Ile342delinsPhe
LRG_504t1:c.1015_1024delGCAAATGATAinsT
LRG_504:g.20620_20629delinsT
LRG_504p1:p.Ala339_Ile342delinsPhe
NC_000001.10:g.241667426_241667435delinsA
NM_000143.3:c.1015_1024delGCAAATGATAinsT

Molecular consequence:

NM_000143.4:c.1015_1024delinsT - inframe_indel - [Sequence Ontology: SO:0001820]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004666100	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 5, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 24684806, 21304509, 22528940, 21051878, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004666100

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 5, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Citations

PubMed

Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas.

Kuwada M, Chihara Y, Lou Y, Torimoto K, Kagebayashi Y, Tamura K, Shuin T, Fujimoto K, Kuniyasu H, Samma S.

BMC Res Notes. 2014 Mar 31;7:203. doi: 10.1186/1756-0500-7-203.

PubMed [citation]

PMID:: 24684806
PMCID:: PMC3978052

Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC.

Yamasaki T, Tran TA, Oz OK, Raj GV, Schwarz RE, Deberardinis RJ, Zhang X, Brugarolas J.

Nat Rev Urol. 2011 Mar;8(3):165-71. doi: 10.1038/nrurol.2010.234. Epub 2011 Feb 8.

PubMed [citation]

PMID:: 21304509
PMCID:: PMC3055922

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004666100.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Asp341 amino acid residue in FH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24684806, 21304509, 22528940, 21051878). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with FH-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.1015_1024delinsT, is a complex sequence change that results in the deletion of 4 and insertion of 1 amino acid(s) in the FH protein (p.Ala339_Ile342delinsPhe).

#	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 29, 2024

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