TRDN : c.1257C>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1257C>A	p.D419E (Asp > Glu)	substitution	missense	chr6:123696766 (reverse strand)	0.13740491

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.13740491 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.14743721 1444 / 9794	0.30149502 726 / 2408	0.11239193 78 / 694	0.07273188 574 / 7892	0.12663755 58 / 458	0.15670732 257 / 1640	0.16800000 42 / 250	0.13740491 3179 / 23136
ESP	0.11883 949 / 7986	0.25693 908 / 3534						0.16120 1857 / 11520
1KG	0.12500 101 / 808	0.31165 412 / 1322	0.06647 67 / 1008	0.04499 44 / 978	0.11960 83 / 694	0.15657 31 / 198		0.14736 738 / 5008

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

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

0.10989 20 / 182 British	0.27049 33 / 122 African-American	0.08065 15 / 186 Chinese Dai	0.04070 7 / 172 Bengali	0.13298 25 / 188 Colombian
0.11215 24 / 214 Iberian	0.25521 49 / 192 African-Caribbean	0.05340 11 / 206 Han, Beijing	0.03883 8 / 206 Gujarati Indian	0.16406 21 / 128 Mexican, LA
0.14953 32 / 214 Toscani	0.31313 62 / 198 Esan, Nigeria	0.01923 4 / 208 Japanese	0.03431 7 / 204 Indian Telugu	0.05882 10 / 170 Peruvian
0.12626 25 / 198 Utah Europeans	0.38053 86 / 226 Gambian	0.12121 24 / 198 Kinh, Vietnam	0.06250 12 / 192 Punjabi, Lahore	0.12981 27 / 208 Puerto Rican
	0.32828 65 / 198 Luhya, Kenya	0.06190 13 / 210 Southern Han	0.04902 10 / 204 Tamil
	0.27059 46 / 170 Mende
	0.32870 71 / 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	ENST00000398178		NM_006073.2
Protein	ENSP00000381240			Q13061

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 0% of algorithms have predicted that this variant will adversely affect protein function
tolerated	conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	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.