DSP : c.4535A>G

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.4535A>G	p.Y1512C (Tyr > Cys)	substitution	missense	chr6:7580958 (forward strand)	0.11560290

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.11560290 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

DCM	OMGL: Detected in 0 / 304 DCM patients. LMM: Detected in 0 / 123 DCM patients.
ARVC	OMGL: Detected in 0 / 352 ARVC patients sequenced at OMGL.

DCM

OMGL: Detected in 0 / 304 DCM patients.

LMM: Detected in 0 / 123 DCM patients.

ARVC

OMGL: Detected in 0 / 352 ARVC patients sequenced at OMGL.

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	0.04545868 3000 / 65994	0.29378698 2979 / 10140	0.29543868 2539 / 8594	0.13995375 2300 / 16434	0.22444367 2582 / 11504	0.06246219 413 / 6612	0.08856502 79 / 892	0.11560290 13892 / 120170
ESP	0.04419 380 / 8600	0.27077 1193 / 4406						0.12094 1573 / 13006
1KG	0.03342 27 / 808	0.31392 415 / 1322	0.28671 289 / 1008	0.15849 155 / 978	0.17723 123 / 694	0.04545 9 / 198		0.20327 1018 / 5008

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

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

0.05495 10 / 182 British	0.23770 29 / 122 African-American	0.27419 51 / 186 Chinese Dai	0.22674 39 / 172 Bengali	0.20745 39 / 188 Colombian
0.00935 2 / 214 Iberian	0.32292 62 / 192 African-Caribbean	0.30583 63 / 206 Han, Beijing	0.12621 26 / 206 Gujarati Indian	0.15625 20 / 128 Mexican, LA
0.03738 8 / 214 Toscani	0.33838 67 / 198 Esan, Nigeria	0.31731 66 / 208 Japanese	0.13725 28 / 204 Indian Telugu	0.23529 40 / 170 Peruvian
0.03535 7 / 198 Utah Europeans	0.37611 85 / 226 Gambian	0.23737 47 / 198 Kinh, Vietnam	0.14062 27 / 192 Punjabi, Lahore	0.11538 24 / 208 Puerto Rican
	0.26263 52 / 198 Luhya, Kenya	0.29524 62 / 210 Southern Han	0.17157 35 / 204 Tamil
	0.32353 55 / 170 Mende
	0.30093 65 / 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	ENST00000379802	LRG_423t1	NM_004415.2
Protein	ENSP00000369129	LRG_423p1		P15924

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	radical	possibly damaging	possibly damaging
LRT	MutationTaster	MutationAssessor	FATHMM
neutral	polymorphism (auto)	neutral	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.