NM_000016.6(ACADM):c.989_1010del (p.Val330fs) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 24, 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:: RCV000548185.7

Allele description [Variation Report for NM_000016.6(ACADM):c.989_1010del (p.Val330fs)]

NM_000016.6(ACADM):c.989_1010del (p.Val330fs)

Gene:

ACADM:acyl-CoA dehydrogenase medium chain [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p31.1

Genomic location:

Preferred name:

NM_000016.6(ACADM):c.989_1010del (p.Val330fs)

HGVS:

NC_000001.11:g.75761165_75761186del
NG_007045.2:g.41808_41829del
NM_000016.6:c.989_1010delMANE SELECT
NM_001127328.3:c.1001_1022del
NM_001286042.2:c.881_902del
NM_001286043.2:c.1088_1109del
NM_001286044.2:c.422_443del
NP_000007.1:p.Val330fs
NP_001120800.1:p.Val334fs
NP_001272971.1:p.Val294fs
NP_001272972.1:p.Val363fs
NP_001272973.1:p.Val141fs
LRG_838:g.41808_41829del
NC_000001.10:g.76226850_76226871del
NM_000016.5:c.989_1010delTTGAACTAGCTAGAATGAGTTA

Protein change:

V141fs

Links:

dbSNP: rs1553127172

NCBI 1000 Genomes Browser:

rs1553127172

Molecular consequence:

NM_000016.6:c.989_1010del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001127328.3:c.1001_1022del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001286042.2:c.881_902del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001286043.2:c.1088_1109del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001286044.2:c.422_443del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Medium-chain acyl-coenzyme A dehydrogenase deficiency (ACADMD)
Synonyms:: CARNITINE DEFICIENCY SECONDARY TO MEDIUM-CHAIN ACYL-CoA DEHYDROGENASE DEFICIENCY; MCADD; Medium chain acyl-CoA dehydrogenase deficiency
Identifiers:: MONDO: MONDO:0008721; MedGen: C0220710; Orphanet: 42; OMIM: 201450

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000630300	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 24, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 8198141, 20434380, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000630300

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 24, 2017)

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

Disease-causing mutations in exon 11 of the medium-chain acyl-CoA dehydrogenase gene.

Andresen BS, Jensen TG, Bross P, Knudsen I, Winter V, Kølvraa S, Bolund L, Ding JH, Chen YT, Van Hove JL, et al.

Am J Hum Genet. 1994 Jun;54(6):975-88.

PubMed [citation]

PMID:: 8198141
PMCID:: PMC1918184

Allelic diversity in MCAD deficiency: the biochemical classification of 54 variants identified during 5 years of ACADM sequencing.

Smith EH, Thomas C, McHugh D, Gavrilov D, Raymond K, Rinaldo P, Tortorelli S, Matern D, Highsmith WE, Oglesbee D.

Mol Genet Metab. 2010 Jul;100(3):241-50. doi: 10.1016/j.ymgme.2010.04.001. Epub 2010 Apr 8.

PubMed [citation]

PMID:: 20434380

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000630300.4

#	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. While this particular variant has not been reported in the literature, loss of function variants in ACADM are known to be pathogenic (PMID: 8198141, 20434380). This sequence change deletes 22 nucleotides from exon 11 of the ACADM mRNA (c.989_1010delTTGAACTAGCTAGAATGAGTTA), causing a frameshift at codon 330. This creates a premature translational stop signal (p.Val330Alafs*32) and is expected to result in an absent or disrupted protein product.

#	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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