TTN : c.19301G>A

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.19301G>Ap.S6434N (Ser > Asn)substitutionmissense chr2:179593352 (reverse strand)0.06986004

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.06986004 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

The role on non-truncating TTN variants in cardiac disease has not yet been analysed in these studies.

Detection in Population Databases



Database European African East Asian South Asian American Finnish Other Total
ExAC0.02748103
1811 / 65900
0.08693852
840 / 9662
0.02558915
215 / 8402
0.17503359
2866 / 16374
0.18910768
2132 / 11274
0.05798654
379 / 6536
0.08202247
73 / 890
0.06986004
8316 / 119038
ESP 0.02462
202 / 8206
0.08338
307 / 3682
0.04282
509 / 11888
1KG
0.02723
22 / 808
0.08699
115 / 1322
0.02381
24 / 1008
0.19121
187 / 978
0.15130
105 / 694
0.07071
14 / 198
0.09325
467 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.03297
6 / 182
British
0.12295
15 / 122
African-American
0.04301
8 / 186
Chinese Dai
0.20930
36 / 172
Bengali
0.14894
28 / 188
Colombian
0.02336
5 / 214
Iberian
0.10417
20 / 192
African-Caribbean
0.01456
3 / 206
Han, Beijing
0.18447
38 / 206
Gujarati Indian
0.17188
22 / 128
Mexican, LA
0.02336
5 / 214
Toscani
0.08081
16 / 198
Esan, Nigeria
0.00000
0 / 208
Japanese
0.19608
40 / 204
Indian Telugu
0.25294
43 / 170
Peruvian
0.03030
6 / 198
Utah Europeans
0.11504
26 / 226
Gambian
0.05556
11 / 198
Kinh, Vietnam
0.14583
28 / 192
Punjabi, Lahore
0.05769
12 / 208
Puerto Rican
0.05051
10 / 198
Luhya, Kenya
0.00952
2 / 210
Southern Han
0.22059
45 / 204
Tamil
0.08824
15 / 170
Mende
0.06019
13 / 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 ENST00000589042 LRG_391t1NM_001267550.1
Protein ENSP00000467141 LRG_391p1

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
50% of algorithms have predicted that this variant will adversely affect protein function
damaging conservative possibly damaging possibly damaging
LRT MutationTaster MutationAssessor FATHMM
polymorphism (auto) medium impact tolerated


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.