LAMA4 : c.1471T>C

Variant Details

Variant (CDS)	Variant (protein)	Variant Type	Variant Effect	Genomic Location (GRCh37)	ExAC Frequency
c.1471T>C	p.Y491H (Tyr > His)	substitution	missense	chr6:112493872 (reverse strand)	0.66491939

Effect in Cardiac Disease

As this variant is present at a population frequency of 0.66491939 (ExAC mean allelic frequency), it is highly unlikely to be pathogenic.

DCM	LMM: Detected in 0 / 121 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	0.60038679 40047 / 66702	0.75091293 7814 / 10406	0.82282004 7096 / 8624	0.79406420 13110 / 16510	0.71396474 8262 / 11572	0.56641452 3744 / 6610	0.66409692 603 / 908	0.66491939 80676 / 121332
ESP	0.60198 5177 / 8600	0.74013 3261 / 4406						0.64878 8438 / 13006
1KG	0.65718 531 / 808	0.77988 1031 / 1322	0.81349 820 / 1008	0.81084 793 / 978	0.72046 500 / 694	0.62121 123 / 198		0.75839 3798 / 5008

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

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

0.60440 110 / 182 British	0.79508 97 / 122 African-American	0.83871 156 / 186 Chinese Dai	0.80814 139 / 172 Bengali	0.68085 128 / 188 Colombian
0.72430 155 / 214 Iberian	0.74479 143 / 192 African-Caribbean	0.73786 152 / 206 Han, Beijing	0.72816 150 / 206 Gujarati Indian	0.75781 97 / 128 Mexican, LA
0.65421 140 / 214 Toscani	0.78788 156 / 198 Esan, Nigeria	0.83173 173 / 208 Japanese	0.84804 173 / 204 Indian Telugu	0.70000 119 / 170 Peruvian
0.63636 126 / 198 Utah Europeans	0.77876 176 / 226 Gambian	0.84343 167 / 198 Kinh, Vietnam	0.82812 159 / 192 Punjabi, Lahore	0.75000 156 / 208 Puerto Rican
	0.80303 159 / 198 Luhya, Kenya	0.81905 172 / 210 Southern Han	0.84314 172 / 204 Tamil
	0.80000 136 / 170 Mende
	0.75926 164 / 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	ENST00000424408	LRG_433t2	NM_002290.3
Protein	ENSP00000416470	LRG_433p2

Missense Variant Predictions
SIFT	Grantham	Polyphen-DIV	Polyphen-VAR	Summary 0% 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	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.