NM_001933.5(DLST):c.1121G>A (p.Gly374Glu) AND Paragangliomas 7

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 17, 2023
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000785999.2

Allele description [Variation Report for NM_001933.5(DLST):c.1121G>A (p.Gly374Glu)]

NM_001933.5(DLST):c.1121G>A (p.Gly374Glu)

Gene:

DLST:dihydrolipoamide S-succinyltransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.3

Genomic location:

Preferred name:

NM_001933.5(DLST):c.1121G>A (p.Gly374Glu)

Other names:

DLST, GLY374GLU (rs1270341616)

HGVS:

NC_000014.9:g.74901127G>A
NG_030313.1:g.24237G>A
NM_001933.5:c.1121G>AMANE SELECT
NP_001924.2:p.Gly374Glu
NC_000014.8:g.75367830G>A
NM_001933.4:c.1121G>A
NR_033814.2:n.1101G>A
NR_045209.2:n.1110G>A

Protein change:

G374E; GLY374GLU

Links:

OMIM: 126063.0001; dbSNP: rs1270341616

NCBI 1000 Genomes Browser:

rs1270341616

Molecular consequence:

NM_001933.5:c.1121G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_033814.2:n.1101G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_045209.2:n.1110G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Paragangliomas 7
Synonyms:: PHEOCHROMOCYTOMA/PARAGANGLIOMA SYNDROME 7
Identifiers:: MONDO: MONDO:0032771; MedGen: C5193116; OMIM: 618475

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000924638	OMIM	no assertion criteria provided	Pathogenic (Oct 17, 2023)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000924638

OMIM

no assertion criteria provided

Pathogenic
(Oct 17, 2023)

germline

literature only

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Recurrent Germline DLST Mutations in Individuals with Multiple Pheochromocytomas and Paragangliomas.

Remacha L, Pirman D, Mahoney CE, Coloma J, Calsina B, Currás-Freixes M, Letón R, Torres-Pérez R, Richter S, Pita G, Herráez B, Cianchetta G, Honrado E, Maestre L, Urioste M, Aller J, García-Uriarte Ó, Gálvez MÁ, Luque RM, Lahera M, Moreno-Rengel C, Eisenhofer G, et al.

Am J Hum Genet. 2019 Apr 4;104(4):651-664. doi: 10.1016/j.ajhg.2019.02.017. Epub 2019 Mar 28. Erratum in: Am J Hum Genet. 2019 May 2;104(5):1008-1010.

PubMed [citation]

PMID:: 30929736
PMCID:: PMC6451733

Details of each submission

From OMIM, SCV000924638.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 4 unrelated patients (patients 3-6) with paragangliomas (PPGL7; 618475), Remacha et al. (2019) identified a germline heterozygous c.1121G-A transition (c.1121G-A, NM_001933) in exon 14 of the DLST gene, resulting in a gly374-to-glu (G374E) substitution at a highly conserved residue in the catalytic domain. The mutation, which was found by targeted next-generation sequencing of candidate genes in the TCA cycle and confirmed by Sanger sequencing, was found in 2 of 123,121 alleles in the gnomAD database. Analysis of tumor tissue from 3 of the patients showed loss of heterozygosity (LOH) for DLST due to uniparental disomy (UPD) in the paternal chromosome. In vitro functional analysis indicated that the mutation impaired catalytic activity of the protein and resulted in abnormal accumulation of the oncometabolite 2HG.

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

Last Updated: Oct 28, 2023

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