TTN : c.64208C>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.64208C>T	p.T21403I (Thr > Ile)	substitution	missense	chr2:179451420 (reverse strand)	0.35088840

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.35088840 (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
ExAC	0.23012684 15349 / 66698	0.53010819 5194 / 9798	0.70272492 5983 / 8514	0.52507267 8670 / 16512	0.43203125 4977 / 11520	0.27676951 1830 / 6612	0.33111111 298 / 900	0.35088840 42301 / 120554
ESP	0.21968 1837 / 8362	0.50809 2009 / 3954						0.31228 3846 / 12316
1KG	0.23391 189 / 808	0.55825 738 / 1322	0.72123 727 / 1008	0.55624 544 / 978	0.40778 283 / 694	0.30808 61 / 198		0.50759 2542 / 5008

View sub-population details for 1000 Genomes (1KG) data

Hide sub-population details for 1000 Genomes (1KG) data

0.23077 42 / 182 British	0.50000 61 / 122 African-American	0.84409 157 / 186 Chinese Dai	0.65116 112 / 172 Bengali	0.39362 74 / 188 Colombian
0.23832 51 / 214 Iberian	0.54688 105 / 192 African-Caribbean	0.66019 136 / 206 Han, Beijing	0.50971 105 / 206 Gujarati Indian	0.38281 49 / 128 Mexican, LA
0.26168 56 / 214 Toscani	0.63636 126 / 198 Esan, Nigeria	0.63942 133 / 208 Japanese	0.54902 112 / 204 Indian Telugu	0.51176 87 / 170 Peruvian
0.20202 40 / 198 Utah Europeans	0.56637 128 / 226 Gambian	0.74747 148 / 198 Kinh, Vietnam	0.53646 103 / 192 Punjabi, Lahore	0.35096 73 / 208 Puerto Rican
	0.51515 102 / 198 Luhya, Kenya	0.72857 153 / 210 Southern Han	0.54902 112 / 204 Tamil
	0.51765 88 / 170 Mende
	0.59259 128 / 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_391t1	NM_001267550.1
Protein	ENSP00000467141	LRG_391p1

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 12.5% of algorithms have predicted that this variant will adversely affect protein function
damaging	moderately conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
	polymorphism (auto)	neutral	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.