NM_001103.4(ACTN2):c.350_351delinsCC (p.Ile117Thr) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 21, 2021
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:: RCV002023020.2

Allele description [Variation Report for NM_001103.4(ACTN2):c.350_351delinsCC (p.Ile117Thr)]

NM_001103.4(ACTN2):c.350_351delinsCC (p.Ile117Thr)

Gene:

ACTN2:actinin alpha 2 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_001103.4(ACTN2):c.350_351delinsCC (p.Ile117Thr)

HGVS:

NC_000001.11:g.236719002_236719003delinsCC
NG_009081.2:g.59862_59863delinsCC
NM_001103.4:c.350_351delinsCCMANE SELECT
NM_001278343.2:c.350_351delinsCC
NM_001278344.2:c.-472_-471delinsCC
NP_001094.1:p.Ile117Thr
NP_001265272.1:p.Ile117Thr
LRG_436t1:c.350_351delinsCC
LRG_436:g.59862_59863delinsCC
LRG_436p1:p.Ile117Thr
NC_000001.10:g.236882302_236882303delinsCC
NG_009081.1:g.37533T>C

Protein change:

I117T

Links:

dbSNP: rs2102894975

NCBI 1000 Genomes Browser:

rs2102894975

Molecular consequence:

NM_001278344.2:c.-472_-471delinsCC - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001103.4:c.350_351delinsCC - missense variant - [Sequence Ontology: SO:0001583]
NM_001278343.2:c.350_351delinsCC - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002305215	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 21, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002305215

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 21, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV002305215.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces isoleucine with threonine at codon 117 of the ACTN2 protein (p.Ile117Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. The frequency data for this variant in the population databases is not available, as this variant may be reported as separate entries in the ExAC database. This variant has not been reported in the literature in individuals with ACTN2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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