GCKR : c.1337T>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1337T>C	p.L446P (Leu > Pro)	substitution	missense	chr2:27730940 (forward strand)	0.64285007

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.64285007 (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	0.58924660 39278 / 66658	0.86464142 8994 / 10402	0.50614564 4365 / 8624	0.76047977 12554 / 16508	0.67858380 7839 / 11552	0.65448757 4317 / 6596	0.65783664 596 / 906	0.64285007 77943 / 121246
ESP	0.58314 5015 / 8600	0.85701 3776 / 4406						0.67592 8791 / 13006
1KG	0.56312 455 / 808	0.90620 1198 / 1322	0.51885 523 / 1008	0.79959 782 / 978	0.63833 443 / 694	0.69697 138 / 198		0.70667 3539 / 5008

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

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

0.63187 115 / 182 British	0.90164 110 / 122 African-American	0.63978 119 / 186 Chinese Dai	0.77907 134 / 172 Bengali	0.56383 106 / 188 Colombian
0.57009 122 / 214 Iberian	0.88542 170 / 192 African-Caribbean	0.40777 84 / 206 Han, Beijing	0.79126 163 / 206 Gujarati Indian	0.64844 83 / 128 Mexican, LA
0.49065 105 / 214 Toscani	0.89899 178 / 198 Esan, Nigeria	0.41827 87 / 208 Japanese	0.83824 171 / 204 Indian Telugu	0.67647 115 / 170 Peruvian
0.57071 113 / 198 Utah Europeans	0.94690 214 / 226 Gambian	0.64646 128 / 198 Kinh, Vietnam	0.76042 146 / 192 Punjabi, Lahore	0.66827 139 / 208 Puerto Rican
	0.88889 176 / 198 Luhya, Kenya	0.50000 105 / 210 Southern Han	0.82353 168 / 204 Tamil
	0.91765 156 / 170 Mende
	0.89815 194 / 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	ENST00000264717		NM_001486.3
Protein	ENSP00000264717

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