Table 3.
Agreement Between Human Gene Mutation Database and Multidisciplinary Genomics Team Classification for 574 Unique, Previously Described, Inherited Disease Risk Candidates Found in 12 Participants by Whole-Genome Sequencing
| HGMD Genomics Teama | No. (%) of Total Variants for Each HGMD Classification | Total | |||||
|---|---|---|---|---|---|---|---|
| Disease-Causing Mutation | Likely Disease Causing Mutation | Disease Associated Functional Polymorphism | Disease Associated Polymorphism | Functional Polymorphism | Frame Shift or Truncating Variantb | ||
| Not associated with an inherited disease | 1 (1.4) | 44 (67.8) | 111 (84.1) | 176 (75.9) | 64 (88.9) | 0 | 396 |
| Likely benign, strong evidence | 1 (1.4) | 0 | 5 (3.8) | 19 (8.2) | 1 (1.4) | 5 (100.0) | 31 |
| Some evidence suggesting benign | 17 (25.0) | 10 (15.4) | 4 (3.0) | 17 (7.3) | 3 (4.2) | 0 | 51 |
| Uncertain significance | 29 (42.6) | 9 (13.8) | 8 (6.1) | 17 (7.3) | 1 (1.4) | 0 | 64 |
| Some evidence suggesting pathogenic | 4 (5.9) | 1 (1.5) | 2 (1.5) | 2 (0.9) | 3 (4.2) | 0 | 12 |
| Likely pathogenic | 8 (11.8) | 0 | 0 | 1 (0.4) | 0 | 0 | 9 |
| Very likely pathogenic | 8 (11.8) | 1 (1.5) | 2 (1.5) | 0 | 0 | 0 | 11 |
| Total | 68 | 65 | 132 | 232 | 72 | 5 | 574 |
Abbreviations: HGMD, Human Gene Mutation Database.
All variants cataloged in HGMD are, by definition, previously reported. Thus, the categories from Table S1 (in the Supplement) “Novel, predicted benign,” “Novel, predicted damaging by one program”, and “Novel, predicted damaging by two or more programs” do not apply and are not displayed.
Polymorphic or rare variant reported in the literature (eg, detected in the process of whole-genome/exome screening) that is predicted to truncate or otherwise alter the gene product but with no disease association reported as yet.