TTN : c.31864G>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.31864G>A	p.G10622R (Gly > Arg)	substitution	missense	chr2:179554305 (reverse strand)	0.39948200

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.39948200 (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	0.36966372 20886 / 56500	0.61116052 5498 / 8996	0.17825965 1266 / 7102	0.46526743 6872 / 14770	0.36220044 3325 / 9180	0.51813133 3172 / 6122	0.39427861 317 / 804	0.39948200 41336 / 103474
ESP	0.36045 2955 / 8198	0.59488 2207 / 3710						0.43349 5162 / 11908
1KG	0.35767 289 / 808	0.60666 802 / 1322	0.16766 169 / 1008	0.48160 471 / 978	0.35014 243 / 694	0.48485 96 / 198		0.41334 2070 / 5008

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

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

0.39560 72 / 182 British	0.58197 71 / 122 African-American	0.18280 34 / 186 Chinese Dai	0.52907 91 / 172 Bengali	0.39362 74 / 188 Colombian
0.33645 72 / 214 Iberian	0.63021 121 / 192 African-Caribbean	0.15049 31 / 206 Han, Beijing	0.47573 98 / 206 Gujarati Indian	0.38281 49 / 128 Mexican, LA
0.29439 63 / 214 Toscani	0.65152 129 / 198 Esan, Nigeria	0.12019 25 / 208 Japanese	0.47549 97 / 204 Indian Telugu	0.35294 60 / 170 Peruvian
0.41414 82 / 198 Utah Europeans	0.61504 139 / 226 Gambian	0.20707 41 / 198 Kinh, Vietnam	0.44792 86 / 192 Punjabi, Lahore	0.28846 60 / 208 Puerto Rican
	0.57576 114 / 198 Luhya, Kenya	0.18095 38 / 210 Southern Han	0.48529 99 / 204 Tamil
	0.58824 100 / 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 25% of algorithms have predicted that this variant will adversely affect protein function
damaging	moderately radical
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.