PCSK9 : c.1420G>A

PCSK9 gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.1420G>Ap.V474I (Val > Ile)substitutionmissense chr1:55524237 (forward strand)0.85443528

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.85443528 (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
ExAC0.83268833
55512 / 66666		0.78534284
8155 / 10384		0.99144113
8572 / 8646		0.87512112
14450 / 16512		0.92439952
10699 / 11574		0.82552162
5460 / 6614		0.87942478
795 / 904		0.85443528
103643 / 121300
ESP 0.83349
7168 / 8600		 0.78711
3468 / 4406		 0.81778
10636 / 13006
1KG
 0.82302
665 / 808		 0.77458
1024 / 1322		 0.98810
996 / 1008		 0.90491
885 / 978		 0.89481
621 / 694		 0.81313
161 / 198		 0.86901
4352 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.81868
149 / 182
British
0.81967
100 / 122
African-American
1.00000
186 / 186
Chinese Dai
0.91860
158 / 172
Bengali
0.85638
161 / 188
Colombian
0.80841
173 / 214
Iberian
0.78646
151 / 192
African-Caribbean
1.00000
206 / 206
Han, Beijing
0.92718
191 / 206
Gujarati Indian
0.94531
121 / 128
Mexican, LA
0.84112
180 / 214
Toscani
0.81818
162 / 198
Esan, Nigeria
0.95192
198 / 208
Japanese
0.91667
187 / 204
Indian Telugu
0.93529
159 / 170
Peruvian
0.82323
163 / 198
Utah Europeans
0.69912
158 / 226
Gambian
0.99495
197 / 198
Kinh, Vietnam
0.85417
164 / 192
Punjabi, Lahore
0.86538
180 / 208
Puerto Rican
0.72222
143 / 198
Luhya, Kenya
0.99524
209 / 210
Southern Han
0.90686
185 / 204
Tamil
0.81176
138 / 170
Mende
0.79630
172 / 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 ENST00000302118 LRG_275t1NM_174936.3
Protein ENSP00000303208 LRG_275p1Q8NBP7

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) 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.