WNK1 : c.1994C>T

WNK1 gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.1994C>Tp.T665I (Thr > Ile)substitutionmissense chr12:971291 (forward strand)0.06388710

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.06388710 (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
ExAC0.07236842
4829 / 66728		0.01201230
125 / 10406		0.09209614
797 / 8654		0.02713178
448 / 16512		0.07720906
893 / 11566		0.09029038
597 / 6612		0.07268722
66 / 908		0.06388710
7755 / 121386
ESP 0.07535
648 / 8600		 0.01657
73 / 4406		 0.05544
721 / 13006
1KG
 0.09653
78 / 808		 0.00454
6 / 1322		 0.09425
95 / 1008		 0.02965
29 / 978		 0.08213
57 / 694		 0.10101
20 / 198		 0.05691
285 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.07143
13 / 182
British
0.02459
3 / 122
African-American
0.14516
27 / 186
Chinese Dai
0.04070
7 / 172
Bengali
0.06383
12 / 188
Colombian
0.08879
19 / 214
Iberian
0.01042
2 / 192
African-Caribbean
0.09709
20 / 206
Han, Beijing
0.02427
5 / 206
Gujarati Indian
0.06250
8 / 128
Mexican, LA
0.13084
28 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.07692
16 / 208
Japanese
0.01471
3 / 204
Indian Telugu
0.12941
22 / 170
Peruvian
0.09091
18 / 198
Utah Europeans
0.00442
1 / 226
Gambian
0.06566
13 / 198
Kinh, Vietnam
0.04688
9 / 192
Punjabi, Lahore
0.07212
15 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.09048
19 / 210
Southern Han
0.02451
5 / 204
Tamil
0.00000
0 / 170
Mende
0.00000
0 / 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 ENST00000315939 NM_018979.3
Protein ENSP00000313059 Q9H4A3

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