NM_000016.5(ACADM):c.734C>T (p.Ser245Leu) AND not provided

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Nov 15, 2016)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000077894.7

Allele description [Variation Report for NM_000016.5(ACADM):c.734C>T (p.Ser245Leu)]

NM_000016.5(ACADM):c.734C>T (p.Ser245Leu)

Gene:
ACADM:acyl-CoA dehydrogenase medium chain [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p31.1
Genomic location:
Preferred name:
NM_000016.5(ACADM):c.734C>T (p.Ser245Leu)
Other names:
S220L
HGVS:
  • NC_000001.11:g.75749444C>T
  • NG_007045.2:g.30087C>T
  • NM_000016.5:c.734C>T
  • NM_001127328.2:c.746C>T
  • NM_001286042.1:c.626C>T
  • NM_001286043.1:c.833C>T
  • NM_001286044.1:c.167C>T
  • NP_000007.1:p.Ser245Leu
  • NP_000007.1:p.Ser245Leu
  • NP_000007.1:p.Ser245Leu
  • NP_001120800.1:p.Ser249Leu
  • NP_001272971.1:p.Ser209Leu
  • NP_001272972.1:p.Ser278Leu
  • NP_001272973.1:p.Ser56Leu
  • LRG_838t1:c.734C>T
  • LRG_838:g.30087C>T
  • LRG_838p1:p.Ser245Leu
  • NC_000001.10:g.76215129C>T
  • NM_000016.4:c.734C>T
  • P11310:p.Ser245Leu
Protein change:
S209L; SER220LEU
Links:
UniProtKB: P11310#VAR_013699; OMIM: 607008.0012; dbSNP: rs121434281
NCBI 1000 Genomes Browser:
rs121434281
Molecular consequence:
  • NM_000016.5:c.734C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127328.2:c.746C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001286042.1:c.626C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001286043.1:c.833C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001286044.1:c.167C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000232889EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Aug 19, 2013)
germlineclinical testing

Citation Link,

SCV000511259Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinicscriteria provided, single submitter
Pathogenic
(Jul 20, 2016)
germlineclinical testing

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

SCV000511934GeneDxcriteria provided, single submitter
Likely pathogenic
(Nov 15, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown2not providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000232889.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided2not providednot providednot provided

From Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics, SCV000511259.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot provided0.000164not providednot provided

From GeneDx, SCV000511934.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The S245L missense variant in the ACADM gene has been reported previously in a patient who was homozygous for the S245L variant and who was detected by newborn screening for medium chain acyl-CoA dehydrogenase (MCAD) deficiency. This patient had enzyme studies that showed residual MCAD activity between classical" MCAD deficiency and heterozygous carriers of MCAD deficiency (Zschocke et al., 2001). This variant has also been described in another patient who was compound heterozygous for S245L and another variant; this individual was reported to have significantly higher residual MCAD enzyme activity (Touw et al., 2013). The S245L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded."

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2021

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