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NM_001103.4(ACTN2):c.1484C>A (p.Thr495Lys) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 22, 2017
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:
RCV000531364.7

Allele description

NM_001103.4(ACTN2):c.1484C>A (p.Thr495Lys)

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.1484C>A (p.Thr495Lys)
HGVS:
  • NC_000001.11:g.236747744C>A
  • NG_009081.2:g.88604C>A
  • NM_001103.4:c.1484C>AMANE SELECT
  • NM_001278343.2:c.1484C>A
  • NM_001278344.2:c.860C>A
  • NP_001094.1:p.Thr495Lys
  • NP_001094.1:p.Thr495Lys
  • NP_001265272.1:p.Thr495Lys
  • NP_001265273.1:p.Thr287Lys
  • LRG_436t1:c.1484C>A
  • LRG_436:g.88604C>A
  • LRG_436p1:p.Thr495Lys
  • NC_000001.10:g.236911044C>A
  • NG_009081.1:g.66275C>A
  • NM_001103.3:c.1484C>A
Protein change:
T287K
Links:
dbSNP: rs200248944
NCBI 1000 Genomes Browser:
rs200248944
Molecular consequence:
  • NM_001103.4:c.1484C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278343.2:c.1484C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001278344.2:c.860C>A - 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
SCV000636937Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 22, 2017) 		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 Invitae, SCV000636937.5

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a ACTN2-related disease. This sequence change replaces threonine with lysine at codon 495 of the ACTN2 protein (p.Thr495Lys). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and lysine.

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

Last Updated: Mar 5, 2024