RYR1 : c.6178G>T

RYR1 gene summary

Variant Details

Variant (CDS)Variant (protein)Variant Type Variant EffectGenomic Location (GRCh37)ExAC Frequency
c.6178G>Tp.G2060C (Gly > Cys)substitutionmissense chr19:38983180 (forward strand)0.06937017

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.06937017 (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
ExAC0.06875056
4577 / 66574		0.01119259
116 / 10364		0.00346741
30 / 8652		0.15663234
2586 / 16510		0.07833305
906 / 11566		0.01921913
127 / 6608		0.07095344
64 / 902		0.06937017
8406 / 121176
ESP 0.07128
613 / 8600		 0.01271
56 / 4406		 0.05144
669 / 13006
1KG
 0.07673
62 / 808		 0.00151
2 / 1322		 0.00794
8 / 1008		 0.16973
166 / 978		 0.04899
34 / 694		 0.01515
3 / 198		 0.05491
275 / 5008
View sub-population details for 1000 Genomes (1KG) data
Hide sub-population details for 1000 Genomes (1KG) data

0.06593
12 / 182
British
0.01639
2 / 122
African-American
0.01075
2 / 186
Chinese Dai
0.15116
26 / 172
Bengali
0.05319
10 / 188
Colombian
0.06542
14 / 214
Iberian
0.00000
0 / 192
African-Caribbean
0.00485
1 / 206
Han, Beijing
0.16990
35 / 206
Gujarati Indian
0.04688
6 / 128
Mexican, LA
0.10748
23 / 214
Toscani
0.00000
0 / 198
Esan, Nigeria
0.01442
3 / 208
Japanese
0.13725
28 / 204
Indian Telugu
0.01765
3 / 170
Peruvian
0.06566
13 / 198
Utah Europeans
0.00000
0 / 226
Gambian
0.00505
1 / 198
Kinh, Vietnam
0.21354
41 / 192
Punjabi, Lahore
0.07212
15 / 208
Puerto Rican
0.00000
0 / 198
Luhya, Kenya
0.00476
1 / 210
Southern Han
0.17647
36 / 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 ENST00000359596 NM_000540.2
Protein ENSP00000352608 P21817

Missense Variant Predictions
SIFT Grantham Polyphen-DIV Polyphen-VAR Summary
25% of algorithms have predicted that this variant will adversely affect protein function
tolerated radical possibly damaging benign
LRT MutationTaster MutationAssessor FATHMM
unknown polymorphism 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.