TTN : c.56101A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.56101A>G	p.N18701D (Asn > Asp)	substitution	missense	chr2:179464527 (reverse strand)	0.35535376

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.35535376 (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	0.23396021 15476 / 66148	0.54246828 5301 / 9772	0.70619785 5925 / 8390	0.53295483 8636 / 16204	0.43472539 4955 / 11398	0.27830189 1829 / 6572	0.33483146 298 / 890	0.35535376 42420 / 119374
ESP	0.22606 1846 / 8166	0.53312 1980 / 3714						0.32205 3826 / 11880
1KG	0.24010 194 / 808	0.56884 752 / 1322	0.72520 731 / 1008	0.55930 547 / 978	0.40778 283 / 694	0.30808 61 / 198		0.51278 2568 / 5008

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

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

0.23626 43 / 182 British	0.50820 62 / 122 African-American	0.84409 157 / 186 Chinese Dai	0.65116 112 / 172 Bengali	0.39362 74 / 188 Colombian
0.24299 52 / 214 Iberian	0.55208 106 / 192 African-Caribbean	0.66019 136 / 206 Han, Beijing	0.50971 105 / 206 Gujarati Indian	0.38281 49 / 128 Mexican, LA
0.26636 57 / 214 Toscani	0.63636 126 / 198 Esan, Nigeria	0.65385 136 / 208 Japanese	0.55392 113 / 204 Indian Telugu	0.51176 87 / 170 Peruvian
0.21212 42 / 198 Utah Europeans	0.56637 128 / 226 Gambian	0.74747 148 / 198 Kinh, Vietnam	0.54688 105 / 192 Punjabi, Lahore	0.35096 73 / 208 Puerto Rican
	0.57071 113 / 198 Luhya, Kenya	0.73333 154 / 210 Southern Han	0.54902 112 / 204 Tamil
	0.51765 88 / 170 Mende
	0.59722 129 / 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	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.