OBSCN : c.13467C>A

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.13467C>A	p.H4489Q (His > Gln)	substitution	missense	chr1:228504591 (forward strand)	0.24437234

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.24437234 (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	0.26735469 5492 / 20542	0.22526316 642 / 2850	0.24095238 506 / 2100	0.12669584 1158 / 9140	0.43325387 1454 / 3356	0.27043478 311 / 1150	0.24838710 77 / 310	0.24437234 9640 / 39448
ESP	0.16718 1406 / 8410	0.15734 675 / 4290						0.16386 2081 / 12700
1KG	0.15718 127 / 808	0.12103 160 / 1322	0.15179 153 / 1008	0.09407 92 / 978	0.23487 163 / 694	0.16667 33 / 198		0.14537 728 / 5008

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

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

0.16484 30 / 182 British	0.13934 17 / 122 African-American	0.15591 29 / 186 Chinese Dai	0.11047 19 / 172 Bengali	0.23936 45 / 188 Colombian
0.16355 35 / 214 Iberian	0.15104 29 / 192 African-Caribbean	0.13107 27 / 206 Han, Beijing	0.08738 18 / 206 Gujarati Indian	0.26562 34 / 128 Mexican, LA
0.14486 31 / 214 Toscani	0.13131 26 / 198 Esan, Nigeria	0.16346 34 / 208 Japanese	0.04412 9 / 204 Indian Telugu	0.25882 44 / 170 Peruvian
0.15657 31 / 198 Utah Europeans	0.11062 25 / 226 Gambian	0.17172 34 / 198 Kinh, Vietnam	0.13021 25 / 192 Punjabi, Lahore	0.19231 40 / 208 Puerto Rican
	0.11616 23 / 198 Luhya, Kenya	0.13810 29 / 210 Southern Han	0.10294 21 / 204 Tamil
	0.13529 23 / 170 Mende
	0.07870 17 / 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	ENST00000284548	LRG_412t1	NM_052843.2
Protein	ENSP00000284548	LRG_412p1

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 25% of algorithms have predicted that this variant will adversely affect protein function
tolerated	conservative	probably damaging
LRT	MutationTaster	MutationAssessor	FATHMM
deleterious	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.