NM_001103.4(ACTN2):c.1940A>G (p.Asn647Ser) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 11, 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:
RCV002003059.6

Allele description [Variation Report for NM_001103.4(ACTN2):c.1940A>G (p.Asn647Ser)]

NM_001103.4(ACTN2):c.1940A>G (p.Asn647Ser)

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.1940A>G (p.Asn647Ser)
HGVS:
  • NC_000001.11:g.236754047A>G
  • NG_009081.2:g.94907A>G
  • NM_001103.4:c.1940A>GMANE SELECT
  • NM_001278343.2:c.1940A>G
  • NM_001278344.2:c.1316A>G
  • NP_001094.1:p.Asn647Ser
  • NP_001265272.1:p.Asn647Ser
  • NP_001265273.1:p.Asn439Ser
  • LRG_436t1:c.1940A>G
  • LRG_436:g.94907A>G
  • LRG_436p1:p.Asn647Ser
  • NC_000001.10:g.236917347A>G
  • NG_009081.1:g.72578A>G
Protein change:
N439S
Links:
dbSNP: rs2102942643
NCBI 1000 Genomes Browser:
rs2102942643
Molecular consequence:
  • NM_001103.4:c.1940A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278343.2:c.1940A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278344.2:c.1316A>G - 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
SCV002277095Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Nov 11, 2020) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002277095.3

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ACTN2 protein function. This variant has not been reported in the literature in individuals with ACTN2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces asparagine with serine at codon 647 of the ACTN2 protein (p.Asn647Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine.

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

Last Updated: Sep 29, 2024