ABCC8 : c.4105G>T

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.4105G>T	p.A1369S (Ala > Ser)	substitution	missense	chr11:17418477 (reverse strand)	0.64305177

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.64305177 (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	0.62459090 41604 / 66610	0.93816118 9755 / 10398	0.62055336 5338 / 8602	0.61545917 10160 / 16508	0.60941828 7040 / 11552	0.52157943 3408 / 6534	0.63465784 575 / 906	0.64305177 77880 / 121110
ESP	0.63941 5490 / 8586	0.93205 4101 / 4400						0.73856 9591 / 12986
1KG	0.66832 540 / 808	0.97504 1289 / 1322	0.63889 644 / 1008	0.58487 572 / 978	0.69308 481 / 694	0.56566 112 / 198		0.72644 3638 / 5008

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

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

0.73626 134 / 182 British	0.84426 103 / 122 African-American	0.75269 140 / 186 Chinese Dai	0.58140 100 / 172 Bengali	0.79255 149 / 188 Colombian
0.61682 132 / 214 Iberian	0.94271 181 / 192 African-Caribbean	0.61165 126 / 206 Han, Beijing	0.56311 116 / 206 Gujarati Indian	0.58594 75 / 128 Mexican, LA
0.70561 151 / 214 Toscani	1.00000 198 / 198 Esan, Nigeria	0.61058 127 / 208 Japanese	0.56863 116 / 204 Indian Telugu	0.68235 116 / 170 Peruvian
0.62121 123 / 198 Utah Europeans	0.99115 224 / 226 Gambian	0.65152 129 / 198 Kinh, Vietnam	0.55208 106 / 192 Punjabi, Lahore	0.67788 141 / 208 Puerto Rican
	0.99495 197 / 198 Luhya, Kenya	0.58095 122 / 210 Southern Han	0.65686 134 / 204 Tamil
	1.00000 170 / 170 Mende
	1.00000 216 / 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	ENST00000389817		NM_000352.3
Protein	ENSP00000374467			Q09428

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 12.5% of algorithms have predicted that this variant will adversely affect protein function
tolerated	moderately conservative	benign	benign
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	neutral	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.