LAMP2 non-truncating variants in HCM cohorts


The table below lists the 6 rare (MAF<0.0001 in ExAC) non-truncating LAMP2 variants identified in a cohort of 2451 HCM patients. When this rare variant frequency of 0.00245 is compared with a background population rate of 0.00198, there is a case excess of 0.00047, although this is not statistically significant for non-truncating LAMP2 variants in HCM (p=0.5454).


Variant Type:      All protein-altering variants     -     Truncating variants     -     Non-Truncating variants
Source:      Combined (OMGL + LMM)     -     OMGL     -     LMM



No. Variant (CDS) Variant (Protein) Variant Type Cases (2451)LMM class ExAC frequency
1. c.928G>A p.V310Imissense 2Pathogenic0.000000
2. c.371C>T p.T124Imissense 1VUS favour benign0.000000
3. c.824A>G p.N275Smissense 1VUS0.000000
4. c.56T>G p.L19Rmissense 1VUS favour pathogenic0.000000
5. c.517G>A p.V173Imissense 1VUS favour benign0.000034

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. 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.