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NM_001103.4(ACTN2):c.331G>A (p.Gly111Arg) AND not specified

Germline classification:
Likely benign (1 submission)
Last evaluated:
May 28, 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:
RCV001193478.1

Allele description [Variation Report for NM_001103.4(ACTN2):c.331G>A (p.Gly111Arg)]

NM_001103.4(ACTN2):c.331G>A (p.Gly111Arg)

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.331G>A (p.Gly111Arg)
HGVS:
  • NC_000001.11:g.236718983G>A
  • NG_009081.2:g.59843G>A
  • NM_001103.4:c.331G>AMANE SELECT
  • NM_001278343.2:c.331G>A
  • NM_001278344.2:c.-491G>A
  • NP_001094.1:p.Gly111Arg
  • NP_001094.1:p.Gly111Arg
  • NP_001265272.1:p.Gly111Arg
  • LRG_436t1:c.331G>A
  • LRG_436:g.59843G>A
  • LRG_436p1:p.Gly111Arg
  • NC_000001.10:g.236882283G>A
  • NG_009081.1:g.37514G>A
  • NM_001103.2:c.331G>A
  • NM_001103.3:c.331G>A
Protein change:
G111R
Links:
dbSNP: rs148628141
NCBI 1000 Genomes Browser:
rs148628141
Molecular consequence:
  • NM_001278344.2:c.-491G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001103.4:c.331G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278343.2:c.331G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001362346Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely benign
(May 28, 2019)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Targeted analysis of whole genome sequence data to diagnose genetic cardiomyopathy.

Golbus JR, Puckelwartz MJ, Dellefave-Castillo L, Fahrenbach JP, Nelakuditi V, Pesce LL, Pytel P, McNally EM.

Circ Cardiovasc Genet. 2014 Dec;7(6):751-759. doi: 10.1161/CIRCGENETICS.113.000578. Epub 2014 Sep 1.

PubMed [citation]
PMID:
25179549
PMCID:
PMC4270910

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362346.1

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

Description

Variant summary: ACTN2 c.331G>A (p.Gly111Arg) results in a non-conservative amino acid change located in the Calponin homology domain (IPR001715) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.6e-05 in 251446 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 2.2 fold of the estimated maximal expected allele frequency for a pathogenic variant in ACTN2 causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. c.331G>A has been reported in the literature to not segregate with disease in a large family affected with dilated Cardiomyopathy in whom a causal variant in a different gene (TTN) was identified (Golbus_2014). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Sep 29, 2024