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NM_005159.5(ACTC1):c.740G>A (p.Gly247Asp) AND Cardiovascular phenotype

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 21, 2022
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:
RCV002386332.2

Allele description [Variation Report for NM_005159.5(ACTC1):c.740G>A (p.Gly247Asp)]

NM_005159.5(ACTC1):c.740G>A (p.Gly247Asp)

Genes:
GJD2-DT:GJD2 divergent transcript [Gene - HGNC]
ACTC1:actin alpha cardiac muscle 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
15q14
Genomic location:
Preferred name:
NM_005159.5(ACTC1):c.740G>A (p.Gly247Asp)
HGVS:
  • NC_000015.10:g.34792158C>T
  • NG_007553.1:g.8569G>A
  • NM_005159.5:c.740G>AMANE SELECT
  • NP_005150.1:p.Gly247Asp
  • LRG_388t1:c.740G>A
  • LRG_388:g.8569G>A
  • NC_000015.9:g.35084359C>T
  • NM_005159.4:c.740G>A
Protein change:
G247D
Links:
dbSNP: rs1566967399
NCBI 1000 Genomes Browser:
rs1566967399
Molecular consequence:
  • NM_005159.5:c.740G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002671255Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jan 21, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Cardiac α-Actin (ACTC1) Gene Mutation Causes Atrial-Septal Defects Associated With Late-Onset Dilated Cardiomyopathy.

Frank D, Yusuf Rangrez A, Friedrich C, Dittmann S, Stallmeyer B, Yadav P, Bernt A, Schulze-Bahr E, Borlepawar A, Zimmermann WH, Peischard S, Seebohm G, Linke WA, Baba HA, Krüger M, Unger A, Usinger P, Frey N, Schulze-Bahr E.

Circ Genom Precis Med. 2019 Aug;12(8):e002491. doi: 10.1161/CIRCGEN.119.002491. Epub 2019 Aug 20.

PubMed [citation]
PMID:
31430208

A cardiac α-actin (ACTC1) p. Gly247Asp mutation inhibits SRF-signaling in vitro in neonatal rat cardiomyocytes.

Rangrez AY, Kilian L, Stiebeling K, Dittmann S, Schulze-Bahr E, Frey N, Frank D.

Biochem Biophys Res Commun. 2019 Oct 20;518(3):500-505. doi: 10.1016/j.bbrc.2019.08.081. Epub 2019 Aug 18.

PubMed [citation]
PMID:
31434612

Details of each submission

From Ambry Genetics, SCV002671255.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.G247D pathogenic mutation (also known as c.740G>A), located in coding exon 4 of the ACTC1 gene, results from a G to A substitution at nucleotide position 740. The glycine at codon 247 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been shown to segregate with disease in a family with atrial septal defects and dilated cardiomyopathy (Frank D et al. Circ Genom Precis Med, 2019 08;12:e002491). Functional and structural studies have suggested this alteration disrupts actin polymerization, which may impair contractility and have a deleterious impact on other cellular processes (Rangrez AY et al. Biochem Biophys Res Commun, 2019 10;518:500-505). In addition, this variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Mar 11, 2025