NEXN variants in HCM cohorts


The table below lists the 8 rare (MAF<0.0001 in ExAC) protein-altering NEXN variants identified in a cohort of 632 HCM patients. When this rare variant frequency of 0.01266 is compared with a background population rate of 0.00756, there is a case excess of 0.00510, although this is not statistically significant for protein-altering NEXN variants in HCM (p=0.1584).


Variant Type:      All protein-altering variants     -     Truncating variants     -     Non-Truncating variants
Source:      LMM



No. Variant (CDS) Variant (Protein) Variant Type Cases (632)LMM class ExAC frequency
1. c.341_342delAA p.Gln114ArgfsX16frameshift 1VUS favour pathogenic (1)0.000000
2. c.1453G>A p.E485Kmissense 1VUS (1)0.000050
3. c.1457C>G p.A486Gmissense 1VUS (1)0.000000
4. c.1366G>A p.G456Rmissense 1VUS (1)0.000008
5. c.893C>G p.T298Rmissense 1VUS favour benign (1)0.000099
6. c.392A>G p.Q131Rmissense 1VUS (1)0.000033
7. c.1937C>A p.P646Qmissense 1VUS (1)0.000000
8. c.1112C>T p.P371Lmissense 1VUS (1)0.000061

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.