CLCNKA : c.247A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.247A>G	p.R83G (Arg > Gly)	substitution	missense	chr1:16351275 (forward strand)	0.56363892

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.56363892 (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	0.55804753 37099 / 66480	0.70416426 7305 / 10374	0.74582947 6438 / 8632	0.55487583 9161 / 16510	0.36440678 4214 / 11564	0.53169548 3506 / 6594	0.56415929 510 / 904	0.56363892 68233 / 121058
ESP	0.55209 4748 / 8600	0.69610 3067 / 4406						0.60088 7815 / 13006
1KG	0.58168 470 / 808	0.72012 952 / 1322	0.76885 775 / 1008	0.62986 616 / 978	0.44669 310 / 694	0.48990 97 / 198		0.64297 3220 / 5008

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

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

0.58791 107 / 182 British	0.68033 83 / 122 African-American	0.80645 150 / 186 Chinese Dai	0.65698 113 / 172 Bengali	0.44681 84 / 188 Colombian
0.57944 124 / 214 Iberian	0.73958 142 / 192 African-Caribbean	0.73786 152 / 206 Han, Beijing	0.68447 141 / 206 Gujarati Indian	0.44531 57 / 128 Mexican, LA
0.61215 131 / 214 Toscani	0.76768 152 / 198 Esan, Nigeria	0.74038 154 / 208 Japanese	0.60294 123 / 204 Indian Telugu	0.29412 50 / 170 Peruvian
0.54545 108 / 198 Utah Europeans	0.72566 164 / 226 Gambian	0.78283 155 / 198 Kinh, Vietnam	0.56771 109 / 192 Punjabi, Lahore	0.57212 119 / 208 Puerto Rican
	0.66667 132 / 198 Luhya, Kenya	0.78095 164 / 210 Southern Han	0.63725 130 / 204 Tamil
	0.70000 119 / 170 Mende
	0.74074 160 / 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	ENST00000331433		NM_004070.3
Protein	ENSP00000332771			P51800

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 25% of algorithms have predicted that this variant will adversely affect protein function
tolerated	moderately radical	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	low impact	damaging

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.