RBM20 : c.3667G>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.3667G>C	p.E1223Q (Glu > Gln)	substitution	missense	chr10:112595719 (forward strand)	0.76368029

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.76368029 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

DCM	LMM: Detected in 0 / 156 DCM patients.

For more information on the clinical significance of this variant, please see the ClinVar entry.

Detection in Population Databases

Database	European	African	East Asian	South Asian	American	Finnish	Other	Total
ExAC	0.86809076 7193 / 8286	0.48449248 1031 / 2128	0.79354839 492 / 620	0.72055240 5322 / 7386	0.80940594 327 / 404	0.91176471 31 / 34	0.79347826 146 / 184	0.76368029 14542 / 19042
ESP	0.87241 2776 / 3182	0.49639 687 / 1384						0.75843 3463 / 4566
1KG	0.86262 697 / 808	0.43343 573 / 1322	0.79563 802 / 1008	0.70348 688 / 978	0.79827 554 / 694	0.89394 177 / 198		0.69708 3491 / 5008

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

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

0.89011 162 / 182 British	0.57377 70 / 122 African-American	0.85484 159 / 186 Chinese Dai	0.69186 119 / 172 Bengali	0.82979 156 / 188 Colombian
0.85514 183 / 214 Iberian	0.50521 97 / 192 African-Caribbean	0.83495 172 / 206 Han, Beijing	0.69903 144 / 206 Gujarati Indian	0.84375 108 / 128 Mexican, LA
0.80374 172 / 214 Toscani	0.46970 93 / 198 Esan, Nigeria	0.71154 148 / 208 Japanese	0.68137 139 / 204 Indian Telugu	0.73529 125 / 170 Peruvian
0.90909 180 / 198 Utah Europeans	0.39381 89 / 226 Gambian	0.79293 157 / 198 Kinh, Vietnam	0.72396 139 / 192 Punjabi, Lahore	0.79327 165 / 208 Puerto Rican
	0.34343 68 / 198 Luhya, Kenya	0.79048 166 / 210 Southern Han	0.72059 147 / 204 Tamil
	0.37059 63 / 170 Mende
	0.43056 93 / 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	ENST00000369519	LRG_382t1	NM_001134363.1
Protein	ENSP00000358532	LRG_382p1		Q5T481

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 50% of algorithms have predicted that this variant will adversely affect protein function
damaging	conservative	possibly damaging	possibly damaging
LRT	MutationTaster	MutationAssessor	FATHMM
	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.