TTN : c.10256G>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.10256G>A	p.S3419N (Ser > Asn)	substitution	missense	chr2:179623758 (reverse strand)	0.85117272

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.85117272 (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	0.92740896 61886 / 66730	0.84496348 8791 / 10404	0.76363425 6581 / 8618	0.78907197 13026 / 16508	0.55006918 6361 / 11564	0.88532526 5852 / 6610	0.86563877 786 / 908	0.85117272 103283 / 121342
ESP	0.93244 8019 / 8600	0.84362 3717 / 4406						0.90235 11736 / 13006
1KG	0.92327 746 / 808	0.83888 1109 / 1322	0.78472 791 / 1008	0.78323 766 / 978	0.67003 465 / 694	0.87879 174 / 198		0.80891 4051 / 5008

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

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

0.92857 169 / 182 British	0.78689 96 / 122 African-American	0.80645 150 / 186 Chinese Dai	0.75581 130 / 172 Bengali	0.75000 141 / 188 Colombian
0.92523 198 / 214 Iberian	0.84375 162 / 192 African-Caribbean	0.77670 160 / 206 Han, Beijing	0.82524 170 / 206 Gujarati Indian	0.64062 82 / 128 Mexican, LA
0.94393 202 / 214 Toscani	0.81313 161 / 198 Esan, Nigeria	0.76923 160 / 208 Japanese	0.77941 159 / 204 Indian Telugu	0.35882 61 / 170 Peruvian
0.89394 177 / 198 Utah Europeans	0.81416 184 / 226 Gambian	0.81313 161 / 198 Kinh, Vietnam	0.78125 150 / 192 Punjabi, Lahore	0.87019 181 / 208 Puerto Rican
	0.86869 172 / 198 Luhya, Kenya	0.76190 160 / 210 Southern Han	0.76961 157 / 204 Tamil
	0.84118 143 / 170 Mende
	0.88426 191 / 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 25% of algorithms have predicted that this variant will adversely affect protein function
damaging	conservative	benign	benign
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.