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NM_001103.4(ACTN2):c.2569G>C (p.Asp857His) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 11, 2023
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:
RCV000197913.7

Allele description [Variation Report for NM_001103.4(ACTN2):c.2569G>C (p.Asp857His)]

NM_001103.4(ACTN2):c.2569G>C (p.Asp857His)

Gene:
ACTN2:actinin alpha 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q43
Genomic location:
Preferred name:
NM_001103.4(ACTN2):c.2569G>C (p.Asp857His)
HGVS:
  • NC_000001.11:g.236762503G>C
  • NG_009081.2:g.103363G>C
  • NM_001103.4:c.2569G>CMANE SELECT
  • NM_001278343.2:c.2569G>C
  • NM_001278344.2:c.1945G>C
  • NP_001094.1:p.Asp857His
  • NP_001094.1:p.Asp857His
  • NP_001265272.1:p.Asp857His
  • NP_001265273.1:p.Asp649His
  • LRG_436t1:c.2569G>C
  • LRG_436:g.103363G>C
  • LRG_436p1:p.Asp857His
  • NC_000001.10:g.236925803G>C
  • NG_009081.1:g.81034G>C
  • NM_001103.2:c.2569G>C
  • NM_001103.3:c.2569G>C
Protein change:
D649H
Links:
dbSNP: rs533267299
NCBI 1000 Genomes Browser:
rs533267299
Molecular consequence:
  • NM_001103.4:c.2569G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278343.2:c.2569G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278344.2:c.1945G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dilated cardiomyopathy 1AA (CMD1AA)
Synonyms:
CARDIOMYOPATHY, DILATED, 1AA, WITH OR WITHOUT LEFT VENTRICULAR NONCOMPACTION; CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 23, WITH OR WITHOUT LEFT VENTRICULAR NONCOMPACTION
Identifiers:
MONDO: MONDO:0012808; MedGen: C2677338; Orphanet: 154; OMIM: 612158
Name:
Primary familial hypertrophic cardiomyopathy (HCM)
Synonyms:
Hereditary ventricular hypertrophy; Idiopathic hypertrophic subaortic stenosis
Identifiers:
MONDO: MONDO:0024573; MeSH: D024741; MedGen: C0949658; OMIM: PS192600

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000254670Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 11, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Investigation of Pathogenic Genes in Chinese sporadic Hypertrophic Cardiomyopathy Patients by Whole Exome Sequencing.

Xu J, Li Z, Ren X, Dong M, Li J, Shi X, Zhang Y, Xie W, Sun Z, Liu X, Dai Q.

Sci Rep. 2015 Nov 17;5:16609. doi: 10.1038/srep16609.

PubMed [citation]
PMID:
26573135
PMCID:
PMC4647833

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]
PMID:
30847666
PMCID:
PMC6533346
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000254670.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 857 of the ACTN2 protein (p.Asp857His). This variant is present in population databases (rs533267299, gnomAD 0.005%). This missense change has been observed in individual(s) with ACTN2-related conditions (PMID: 26573135, 30847666). ClinVar contains an entry for this variant (Variation ID: 216493). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024