LAMP2 non-truncating variants in HCM cohorts


The table below lists the 8 rare (MAF<0.0001 in ExAC) non-truncating LAMP2 variants identified in a cohort of 3290 HCM patients (839 patients from OMGL, 2451 patients from LMM). When this rare variant frequency of 0.00243 is compared with a background population rate of 0.00198, there is a case excess of 0.00045, 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 (3290)OMGL classLMM class ExAC frequency
1. c.928G>A p.V310Imissense 2Pathogenic (2)0.000000
2. c.517G>A p.V173Imissense 2VUS (1)VUS favour benign (1)0.000034
3. c.824A>G p.N275Smissense 1VUS (1)0.000000
4. c.56T>G p.L19Rmissense 1VUS favour pathogenic (1)0.000000
5. c.1058A>C p.Q353Pmissense 1Likely Pathogenic (1)0.000000
6. c.371C>T p.T124Imissense 1VUS favour benign (1)0.000000

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.