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NM_001103.4(ACTN2):c.355G>A (p.Ala119Thr) AND ACTN2-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 19, 2020
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:
RCV001265546.8

Allele description [Variation Report for NM_001103.4(ACTN2):c.355G>A (p.Ala119Thr)]

NM_001103.4(ACTN2):c.355G>A (p.Ala119Thr)

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.355G>A (p.Ala119Thr)
HGVS:
  • NC_000001.11:g.236719007G>A
  • NG_009081.2:g.59867G>A
  • NM_001103.4:c.355G>AMANE SELECT
  • NM_001278343.2:c.355G>A
  • NM_001278344.2:c.-467G>A
  • NP_001094.1:p.Ala119Thr
  • NP_001094.1:p.Ala119Thr
  • NP_001265272.1:p.Ala119Thr
  • LRG_436t1:c.355G>A
  • LRG_436:g.59867G>A
  • LRG_436p1:p.Ala119Thr
  • NC_000001.10:g.236882307G>A
  • NG_009081.1:g.37538G>A
  • NM_001103.2:c.355G>A
  • NM_001103.3:c.355G>A
  • P35609:p.Ala119Thr
Protein change:
A119T; ALA119THR
Links:
UniProtKB: P35609#VAR_071970; OMIM: 102573.0005; dbSNP: rs727502886
NCBI 1000 Genomes Browser:
rs727502886
Molecular consequence:
  • NM_001278344.2:c.-467G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001103.4:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278343.2:c.355G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
ACTN2-related disorder
Synonyms:
ACTN2-related disorders; ACTN2 related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001443696Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Mar 19, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot 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 Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego, SCV001443696.1

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

Description

This variant has been previously reported as a heterozygous change and segregating with disease in families with cardiac phenotype heterogeneity. Phenotypes included dilated cardiomyopathy, left ventricular noncompaction, ventricular fibrillation, and sudden death (PMID: 20022194, 25224718). Functional characterization of the variant demonstrated reduced F-actin binding affinity and altered Z-disc localization and dynamics (PMID: 27287556). It is absent from the gnomAD population database and thus is presumed to be rare. The c.355G>A (p.Ala119Thr) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. ClinVar contains an entry for this variant (Variation ID: 162727). Based on the available evidence, the c.355G>A (p.Ala119Thr) variant is classified as Pathogenic.

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

Last Updated: Nov 10, 2024