NM_000016.6(ACADM):c.985A>G (p.Lys329Glu) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 29, 2020
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:: RCV002512722.9

Allele description [Variation Report for NM_000016.6(ACADM):c.985A>G (p.Lys329Glu)]

NM_000016.6(ACADM):c.985A>G (p.Lys329Glu)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

1p31.1

Genomic location:

Preferred name:

NM_000016.6(ACADM):c.985A>G (p.Lys329Glu)

Other names:

K304E; 985A>G; c.985A>G (p.K304E); p.K329E:AAA>GAA; MC K329e

HGVS:

NC_000001.11:g.75761161A>G
NG_007045.2:g.41804A>G
NM_000016.6:c.985A>GMANE SELECT
NM_000016.6:c.985A>G
NM_001127328.2:c.997A>G
NM_001127328.3:c.997A>G
NM_001286042.2:c.877A>G
NM_001286043.2:c.1084A>G
NM_001286044.2:c.418A>G
NP_000007.1:p.Lys329Glu
NP_001120800.1:p.Lys333Glu
NP_001272971.1:p.Lys293Glu
NP_001272972.1:p.Lys362Glu
NP_001272972.1:p.Lys362Glu
NP_001272973.1:p.Lys140Glu
LRG_838t1:c.985A>G
LRG_838:g.41804A>G
LRG_838p1:p.Lys329Glu
NC_000001.10:g.76226846A>G
NC_000001.11:g.75761161A>G
NM_000016.4:c.985A>G
NM_000016.5:c.985A>G
NM_001127328.1:c.997A>G
NM_001286043.1:c.1084A>G

Protein change:

K140E; LYS304GLU

Links:

OMIM: 607008.0001; dbSNP: rs77931234

NCBI 1000 Genomes Browser:

rs77931234

Molecular consequence:

NM_000016.6:c.985A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127328.3:c.997A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286042.2:c.877A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286043.2:c.1084A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001286044.2:c.418A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003666748	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 29, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 2393404, 9158144, 16291504, 20036593, 23028790 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003666748

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 29, 2020)

germline

clinical testing

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

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

Citations

PubMed

Identification of a common mutation in patients with medium-chain acyl-CoA dehydrogenase deficiency.

Matsubara Y, Narisawa K, Miyabayashi S, Tada K, Coates PM, Bachmann C, Elsas LJ 2nd, Pollitt RJ, Rhead WJ, Roe CR.

Biochem Biophys Res Commun. 1990 Aug 31;171(1):498-505.

PubMed [citation]

PMID:: 2393404

The molecular basis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in compound heterozygous patients: is there correlation between genotype and phenotype?

Andresen BS, Bross P, Udvari S, Kirk J, Gray G, Kmoch S, Chamoles N, Knudsen I, Winter V, Wilcken B, Yokota I, Hart K, Packman S, Harpey JP, Saudubray JM, Hale DE, Bolund L, Kølvraa S, Gregersen N.

Hum Mol Genet. 1997 May;6(5):695-707.

PubMed [citation]

PMID:: 9158144

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV003666748.2

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

Description

The c.985A>G (p.K329E) alteration is located in coding exon 11 of the ACADM gene. This alteration results from an A to G substitution at nucleotide position 985, causing the lysine (K) at amino acid position 329 to be replaced by a glutamic acid (E). Based on data from gnomAD, the G allele has an overall frequency of 0.33% (941/282786) total alleles studied. The highest observed frequency was 0.62% (800/129138) of European (non-Finnish) alleles. This is the most common ACADM mutation in Western Europe population and has been reported in a homozygous state or compound heterozygous with other pathogenic alterations in ACADM in multiple unrelated patients (Matsubara, 1990; Waddell, 2006; Arnold, 2010). This amino acid position is highly conserved in available vertebrate species. Functional analysis on lymphocytes from individuals who are homozygous for the p.K329E alteration showed low enzyme activity (0-8%), and heterozygous carriers of the p.K329E alteration had reduced enzyme activity (12-87%; Sturm, 2012). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as 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: Nov 3, 2024

ClinVar

Relating variation to medicine