ACTN2 : c.690T>A

ACTN2 gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.690T>Ap.D230E (Asp > Glu)substitutionmissense chr1:236894607 (forward strand)0.00009885

Effect in Cardiac Disease

This variant is considered a rare variant, with a population frequency of 0.00009885 (ExAC mean allelic frequency).

HCM

There is no significant excess of rare ACTN2 Non-Truncating variants in HCM (details).

OMGL: Detected in 1 / 807 HCM patients - classified as Class 3-Unknown pathogenicity.

LMM:   Detected in 0 / 632 HCM patients.

DCM

There is no significant excess of rare ACTN2 Non-Truncating variants in DCM (details).

OMGL: Detected in 0 / 305 DCM patients.

LMM:   Detected in 0 / 590 DCM patients.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases



Database European African East Asian South Asian American Finnish Other Total
ExAC0.00016484
11 / 66730		0.00000000
0 / 10404		0.00000000
0 / 8652		0.00000000
0 / 16510		0.00008637
1 / 11578		0.00000000
0 / 6612		0.00000000
0 / 908		0.00009885
12 / 121394
ESP 0.00023
2 / 8600		 0.00000
0 / 4406		 0.00015
2 / 13006
1KG
 0.00124
1 / 808		 0.00000
0 / 1322		 0.00000
0 / 1008		 0.00000
0 / 978		 0.00000
0 / 694		 0.00000
0 / 198		 0.00020
1 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.00000
0 / 182
British
0.00000
0 / 122
African-American
0.00000
0 / 186
Chinese Dai
0.00000
0 / 172
Bengali
0.00000
0 / 188
Colombian
0.00467
1 / 214
Iberian
0.00000
0 / 192
African-Caribbean
0.00000
0 / 206
Han, Beijing
0.00000
0 / 206
Gujarati Indian
0.00000
0 / 128
Mexican, LA
0.00000
0 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.00000
0 / 204
Indian Telugu
0.00000
0 / 170
Peruvian
0.00000
0 / 198
Utah Europeans
0.00000
0 / 226
Gambian
0.00000
0 / 198
Kinh, Vietnam
0.00000
0 / 192
Punjabi, Lahore
0.00000
0 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.00000
0 / 210
Southern Han
0.00000
0 / 204
Tamil
0.00000
0 / 170
Mende
0.00000
0 / 216
Yoruba, Nigeria

The Exome Aggregation Consortium (ExAC) is a database of 60,706 unrelated individuals sequenced as part of various disease-specific and population genetic studies. There is partial overlap between ExAC and 1000 Genomes (1KG) (1,851 of the 2,504 samples in 1KG) and the Exome Sequencing Project (ESP) (3,936 of the 6,500 samples in ESP).


Other Variant & Gene Details

Canonical Sequences
Transcript ENST00000366578 LRG_436t1NM_001103.2
Protein ENSP00000355537 LRG_436p1P35609

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
87.5% of algorithms have predicted that this variant will adversely affect protein function
damaging conservative possibly damaging probably damaging
LRT MutationTaster MutationAssessor FATHMM
deleterious disease-causing medium impact damaging


References

1. Roddy Walsh, Kate L. Thomson, James S. Ware, Birgit H. Funke, Jessica Woodley, Karen J. McGuire, Francesco Mazzarotto, Edward Blair, Anneke Seller, Jenny C. Taylor, Eric V. Minikel, Exome Aggregation Consortium, Daniel G. MacArthur, Martin Farrall, Stuart A. Cook and Hugh Watkins. Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples. Genet Med. 2016 doi:10.1038/gim.2016.90.

2. Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH. The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing. Genet Med. 2014 Aug;16(8):601-8.

3. Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL. Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity. Genet Med. 2015 Nov;17(11):880-8.