LAMP2 variants in HCM cohorts

The table below lists the 21 rare (MAF<0.0001 in ExAC) protein-altering LAMP2 variants identified in a cohort of 3290 HCM patients (839 patients from OMGL, 2451 patients from LMM). When this rare variant frequency of 0.00638 is compared with a background population rate of 0.00198, there is a statistically significant case excess of 0.00440 (p<0.0001), which suggests that approximately 14 of these variants may be pathogenic.

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 (3290)OMGL classLMM class ExAC frequency
1. c.928G>A p.V310Imissense 2Pathogenic (2)0.000000
2. c.973del p.Leu325Trpfs*21frameshift 2Pathogenic (2)0.000000
3. c.517G>A p.V173Imissense 2VUS (1)VUS favour benign (1)0.000034
4. c.1058A>C p.Q353Pmissense 1Likely Pathogenic (1)0.000000
5. c.29del p.Pro10Argfs*10frameshift 1Pathogenic (1)0.000000
6. c.222_223del p.Tyr74*frameshift 1Pathogenic (1)0.000000
7. c.824A>G p.N275Smissense 1VUS (1)0.000000
8. c.183+1G>A essential splice site 1Likely Pathogenic (1)0.000000
9. c.864+1G>T essential splice site 1Pathogenic (1)0.000000
10. c.795C>A p.C265Xnonsense 1Pathogenic (1)0.000000
11. c.56T>G p.L19Rmissense 1VUS favour pathogenic (1)0.000000
12. c.124del p.Leu42Phefs*7frameshift 1Pathogenic (1)0.000000
13. c.877C>T p.R293Xnonsense 1Pathogenic (1)0.000000
14. c.371C>T p.T124Imissense 1VUS favour benign (1)0.000000
15. c.270_274del p.Gln91Argfs*20frameshift 1Pathogenic (1)0.000000
16. c.929-1G>A essential splice site 1Likely Pathogenic (1)0.000000
17. c.929-2A>G essential splice site 1Pathogenic (1)0.000000
18. c.128_129dupAT p.Ala44MetfsX6frameshift 1Pathogenic (1)0.000000


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.