GHR : c.1630A>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1630A>C	p.I544L (Ile > Leu)	substitution	missense	chr5:42719239 (forward strand)	0.44338592

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.44338592 (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	0.45327046 30089 / 66382	0.38884608 4037 / 10382	0.59547038 5127 / 8610	0.46943602 7741 / 16490	0.32470363 3725 / 11472	0.36828528 2427 / 6590	0.47421525 423 / 892	0.44338592 53569 / 120818
ESP	0.46058 3961 / 8600	0.38901 1714 / 4406						0.43634 5675 / 13006
1KG	0.44802 362 / 808	0.37897 501 / 1322	0.56944 574 / 1008	0.46217 452 / 978	0.40058 278 / 694	0.29798 59 / 198		0.44449 2226 / 5008

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

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

0.37912 69 / 182 British	0.37705 46 / 122 African-American	0.52688 98 / 186 Chinese Dai	0.51744 89 / 172 Bengali	0.37234 70 / 188 Colombian
0.45794 98 / 214 Iberian	0.38021 73 / 192 African-Caribbean	0.62621 129 / 206 Han, Beijing	0.45631 94 / 206 Gujarati Indian	0.43750 56 / 128 Mexican, LA
0.51869 111 / 214 Toscani	0.41414 82 / 198 Esan, Nigeria	0.56731 118 / 208 Japanese	0.44608 91 / 204 Indian Telugu	0.35294 60 / 170 Peruvian
0.42424 84 / 198 Utah Europeans	0.36283 82 / 226 Gambian	0.57576 114 / 198 Kinh, Vietnam	0.41667 80 / 192 Punjabi, Lahore	0.44231 92 / 208 Puerto Rican
	0.33838 67 / 198 Luhya, Kenya	0.54762 115 / 210 Southern Han	0.48039 98 / 204 Tamil
	0.35294 60 / 170 Mende
	0.42130 91 / 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	ENST00000230882		NM_000163.4
Protein	ENSP00000230882			P10912

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 37.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated	conservative	possibly damaging	probably damaging
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	high 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.