NM_001100.3(ACTA1):c.984G>C (p.Lys328Asn) AND Nemaline myopathy 3

Clinical significance:Pathogenic (Last evaluated: May 10, 2013)

Review status:(1/4)1 star out of maximum of 4 stars

classified by single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000043506.27

Allele description [Variation Report for NM_001100.3(ACTA1):c.984G>C (p.Lys328Asn)]

Gene:
ACTA1:actin, alpha 1, skeletal muscle [Gene - OMIM]
Variant type:
single nucleotide variant
Cytogenetic location:
1q42.13
Genomic location:
Preferred name:
NM_001100.3(ACTA1):c.984G>C (p.Lys328Asn)
HGVS:
  • NC_000001.11:g.229431727C>G
  • NG_006672.1:g.7370G>C
  • NM_001100.3:c.984G>C
  • NP_001091.1:p.Lys328Asn
  • NC_000001.10:g.229567474C>G
Protein change:
K328N; LYS328ASN
Links:
OMIM: 102610.0016; dbSNP: 398122936
NCBI 1000 Genomes Browser:
rs398122936
Molecular consequence:
  • NM_001100.3:c.984G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Nemaline myopathy 3 (NEM3)
Synonyms:
Nemaline myopathy caused by mutation in the alpha-actin gene
Identifiers:
MedGen: C1834336; OMIM: 161800; Orphanet: 607
Age of onset:
Variable
Prevalence:
1-9 / 100 000 607

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Assertion and evidence details

Submission AccessionSubmitterReview StatusClinical Significance
(Last evaluated)
OriginMethodConsequenceCitations
SCV000067362OMIMPathogenic
(May 10, 2013)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedAlleles observedFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Nemaline myopathy with stiffness and hypertonia associated with an ACTA1 mutation.

Jain RK, Jayawant S, Squier W, Muntoni F, Sewry CA, Manzur A, Quinlivan R, Lillis S, Jungbluth H, Sparrow JC, Ravenscroft G, Nowak KJ, Memo M, Marston SB, Laing NG.

Neurology. 2012 Apr 3;78(14):1100-3. doi: 10.1212/WNL.0b013e31824e8ebe. Epub 2012 Mar 21. No abstract available. Erratum in: Neurology. 2012 May 22;78(21):1704.

PubMed [citation]
PMID:
22442437

Details of each submission

From OMIM, SCV000067362.1

#EthnicityAlleles ObservedChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In an infant with nemaline myopathy-3 (161800) who presented with an atypical phenotype of stiffness and hypertonicity, Jain et al. (2012) identified a de novo heterozygous 984G-C transversion in the ACTA1 gene, resulting in a lys328-to-asn (K328N) substitution (K326N in the mature protein). Patient biopsy showed nemaline bodies and 32% mutant actin. In vitro motility analysis of actin thin filaments derived from the patient's tissue showed increased sensitivity to calcium, indicating an activated state. Expression of the mutant in mouse muscle cells did not result in the formation of rod-like structures, suggesting a different mechanism of nemaline body formation. Medical treatment was ineffective, and the patient died at age 9 months in an asystolic episode. The report expanded the phenotypic spectrum associated with ACTA1 mutations to include stiffness, rigidity, and hypertonicity.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodVariant allelesAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 5, 2014

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