NM_000016.6(ACADM):c.233T>C (p.Ile78Thr) AND Medium-chain acyl-coenzyme A dehydrogenase deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 4, 2019
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:: RCV000178019.4

Allele description

NM_000016.6(ACADM):c.233T>C (p.Ile78Thr)

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.233T>C (p.Ile78Thr)

Other names:

p.I78T:ATT>ACT

HGVS:

NC_000001.11:g.75732869T>C
NG_007045.2:g.13512T>C
NM_000016.6:c.233T>CMANE SELECT
NM_001127328.3:c.245T>C
NM_001286042.2:c.125T>C
NM_001286043.2:c.233T>C
NM_001286044.2:c.-153T>C
NP_000007.1:p.Ile78Thr
NP_001120800.1:p.Ile82Thr
NP_001272971.1:p.Ile42Thr
NP_001272972.1:p.Ile78Thr
LRG_838t1:c.233T>C
LRG_838:g.13512T>C
LRG_838p1:p.Ile78Thr
NC_000001.10:g.76198554T>C
NM_000016.4:c.233T>C
NM_000016.5:c.233T>C
P11310:p.Ile78Thr

Protein change:

I42T

Links:

UniProtKB: P11310#VAR_015954; dbSNP: rs398123074

NCBI 1000 Genomes Browser:

rs398123074

Molecular consequence:

NM_001286044.2:c.-153T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000016.6:c.233T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001127328.3:c.245T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286042.2:c.125T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001286043.2:c.233T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000630281	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 4, 2019)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22630369, 15171998, 16737882, 22542437, 24623196, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000630281

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 4, 2019)

germline

clinical testing

PubMed (6)
[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

Risk stratification by residual enzyme activity after newborn screening for medium-chain acyl-CoA dehyrogenase deficiency: data from a cohort study.

Touw CM, Smit GP, de Vries M, de Klerk JB, Bosch AM, Visser G, Mulder MF, Rubio-Gozalbo ME, Elvers B, Niezen-Koning KE, Wanders RJ, Waterham HR, Reijngoud DJ, Derks TG.

Orphanet J Rare Dis. 2012 May 25;7:30. doi: 10.1186/1750-1172-7-30.

PubMed [citation]

PMID:: 22630369
PMCID:: PMC3543239

Rapid, comprehensive screening of the human medium chain acyl-CoA dehydrogenase gene.

McKinney JT, Longo N, Hahn SH, Matern D, Rinaldo P, Strauss AW, Dobrowolski SF.

Mol Genet Metab. 2004 Jun;82(2):112-20.

PubMed [citation]

PMID:: 15171998

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000630281.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces isoleucine with threonine at codon 78 of the ACADM protein (p.Ile78Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs398123074, ExAC 0.002%). This variant has been reported as homozygous or in combination with other ACADM variants in individuals affected with medium chain acyl-coA dehydrogenase deficiency (PMID: 24623196, 22630369, 15171998, 16737882, 22542437). ClinVar contains an entry for this variant (Variation ID: 92261). Experimental studies have shown that this missense change, as homozygous or co-occurs in trans with c.985A>G (p.Lys329Glu), is associated with severely reduced ACADM enzyme activity in leukocytes or lymphocytes from patients affected with medium chain acyl-coA dehydrogenase deficiency (PMID: 22630369). For these reasons, this variant has been 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: Feb 5, 2022

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