NM_000108.5(DLD):c.1116_1117del (p.Ile372fs) AND Pyruvate dehydrogenase E3 deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 24, 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:: RCV002923317.3

Allele description [Variation Report for NM_000108.5(DLD):c.1116_1117del (p.Ile372fs)]

NM_000108.5(DLD):c.1116_1117del (p.Ile372fs)

Gene:

DLD:dihydrolipoamide dehydrogenase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q31.1

Genomic location:

Preferred name:

NM_000108.5(DLD):c.1116_1117del (p.Ile372fs)

HGVS:

NC_000007.14:g.107917342_107917343del
NG_008045.1:g.31202_31203del
NM_000108.5:c.1116_1117delMANE SELECT
NM_001289750.1:c.819_820del
NM_001289751.1:c.1047_1048del
NM_001289752.1:c.972_973del
NP_000099.2:p.Ile372fs
NP_001276679.1:p.Ile273fs
NP_001276680.1:p.Ile349fs
NP_001276681.1:p.Ile324fs
NC_000007.13:g.107557786_107557787del
NC_000007.13:g.107557787_107557788del

Protein change:

I273fs

Molecular consequence:

NM_000108.5:c.1116_1117del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289750.1:c.819_820del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289751.1:c.1047_1048del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001289752.1:c.972_973del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Pyruvate dehydrogenase E3 deficiency (DLDD)
Synonyms:: MAPLE SYRUP URINE DISEASE, TYPE III; DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; Maple syrup urine disease, type 3; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009529; MedGen: C5574660; Orphanet: 2394; Orphanet: 765; OMIM: 246900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003268547	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8968745, 9934985, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003268547

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2021)

germline

clinical testing

PubMed (3)
[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

Identification of two mutations in a compound heterozygous child with dihydrolipoamide dehydrogenase deficiency.

Hong YS, Kerr DS, Craigen WJ, Tan J, Pan Y, Lusk M, Patel MS.

Hum Mol Genet. 1996 Dec;5(12):1925-30.

PubMed [citation]

PMID:: 8968745

Molecular basis of lipoamide dehydrogenase deficiency in Ashkenazi Jews.

Shaag A, Saada A, Berger I, Mandel H, Joseph A, Feigenbaum A, Elpeleg ON.

Am J Med Genet. 1999 Jan 15;82(2):177-82.

PubMed [citation]

PMID:: 9934985

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003268547.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DLD-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile372Metfs*3) in the DLD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DLD are known to be pathogenic (PMID: 8968745, 9934985).

#	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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