Table 1.
Summary of the clinical features and information of the likely pathogenic and candidate variants classified as VUS identified in this study.
| No. | Sample ID | Gender | Onset Age | Age at Genetic Testing | Fluctuation | Progression | Base Change | AA Change | Domain | Type of HL | Severity | CADD Phred | ACMG Criteria | ACMG Category | MAF in ExAC | MAF in ToMMo | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | SNS5183 | M | 16 | 24 | Yes | No | c.208A>G | p.N70D | Flat | Mild | 24.0 | VUS | PM2, PP3 | - | - | This study | |
| 2 | 4238 | F | Unknown | 49 | No | No | c.494C>T | p.T165I | NIDO | Mid | Mild | 32.0 | VUS | PM1, PM2, PP3 | 0.0000331 | 0.0004 | This study |
| 3 | GNM5012 | F | 5 | 7 | Unknown | Yes | c.589G>A | p.D197N | NIDO | High | Moderate | 27.8 | Likely pathogenic | PM1, PM2, PP1, PP3 | - | - | Hildebrand, 2011 [22]. |
| 4 | 4030 | M | 0 | 10 | No | No | c.605T>C | p.L202P | NIDO | Mid | Mild | 27.0 | Likely pathogenic | PM1, PM2, PP1, PP3 | - | - | This study |
| 5 | HL2684 | F | 6 | 10 | No | Yes | c.1816T>G | p.C606G | ZA (TIL1) | Mid | Mild | 22.3 | Likely pathogenic | PM1, PM2, PP1, PP3 | - | - | This study |
| 6 | HL1389 | F | 6 | 34 | No | No | c.1898G>T | p.C633F | ZA (TIL1) | High | Moderate | 27.6 | VUS | PM1, PM2, PP3 | - | - | This study |
| 7 | HL2875 | F | 7 | 23 | Yes | No | c.2087G>A | p.C696Y | ZA | Flat | Mild | 26.7 | VUS | PM1, PM2, PP3 | - | - | This study |
| 8 | 2803 | M | 25 | 46 | No | No | c.2087G>C | p.C696S | ZA | High | Moderate | 25.6 | VUS | PM1,PM2,PP3 | - | - | This study |
| 9 | 4238 | F | Unknown | 49 | No | No | c.3043G>A | p.E1015K | ZA (TIL2) | Mid | Mild | 26.4 | VUS | PM1,PM2,PP3 | 0.0000165 | 0.0004 | This study |
| 10 | HL1942 | F | 59 | 77 | No | Yes | c.3605C>T | p.S1202F | ZA (VWD3) | Flat | Profound | 24.1 | VUS | PM1, PM2, PP3, BS2 | 0.0000741 | 0.0001 | This study |
| 11 | SNS5351 | F | 12 | 16 | No | No | c.3850C>T | p.R1284C | ZA (VWD3) | High | Mild | 26.1 | Likely pathogenic | PM1, PM2, PM7, PP3 | - | - | This study |
| 12 | HL3514 | M | 6 | 8 | No | No | c.3850C>T | p.R1284C | ZA (VWD3) | Flat | Mild | 26.1 | Likely pathogenic | PM1, PM2, PM7, PP3 | - | - | This study |
| 13 | 2965 | M | 6 | 10 | No | No | c.3995G>A | p.C1332Y | ZA | High | Mild | 24.4 | Likely pathogenic | PM1, PM2, PP1, PP3 | - | - | This study |
| 14 | HL0644 | M | 0 | 16 | No | Yes | c.4495G>C | p.D1499H | ZA (VWD4) | Mid | Moderate | 29.7 | VUS | PM1, PM2, PP3, BS2 | - | 0.0006 | This study |
| 15 | 3552 | M | 62 | 64 | Yes | Yes | c.5372C>G | p.P1791R | Mid | Moderate | 22.5 | VUS | PM2, PP5, BP4 | 0.0002 | - | Hildebrand, 2011 [22]. | |
| 16 | HL4169 | F | 6 | 13 | No | No | c.5597C>T | p.T1866M | ZP | Flat | Mild | 35.0 | Likely pathogenic | PM1, PM2, PM7, PP3, PP5 | 0.00000824 | - | Sagong, 2010 [23]. |
| 17 | HL3681 | M | 0 | 0 | No | No | c.5597C>T | p.T1866M | ZP | Mid | Moderate | 35.0 | Likely pathogenic | PM1, PM2, PM7, PP3, PP5 | 0.00000824 | - | Sagong, 2010 [23]. |
| 18 | HL0605 | M | 0 | 10 | No | No | c.5597C>T | p.T1866M | ZP | Mid | Mild | 35.0 | Likely pathogenic | PM1, PM2, PM7, PP3, PP5 | 0.00000824 | - | Sagong, 2010 [23]. |
| 19 | 2271 | M | Unknown | 6 | Unknown | Unknown | c.5597C>T | p.T1866M | ZP | Mid | Moderate | 35.0 | Likely pathogenic | PM1, PM2, PM7, PP3, PP5 | 0.00000824 | - | Sagong, 2010 [23]. |
| 20 | HL3110 | F | Unknown | 82 | No | Yes | c.5668C>T | p.R1890C | ZP | Flat | Severe | 34.0 | Likely pathogenic | PM1, PM2, PP3, PP5 | - | - | Plantinga, 2006 [5]. |
| 21 | 2787 | F | 15 | 27 | Unknown | Yes | c.5668C>T | p.R1890C | ZP | Mid | Mild | 34.0 | Likely pathogenic | PM1, PM2, PP3, PP5 | - | - | Plantinga, 2006 [5]. |
| 22 | HL0950 | F | 3 | 4 | No | No | c.5807T>C | p.L1936P | ZP | unspecified | Moderate | 25.4 | Likely pathogenic | PM1, PM2, PP1, PP3 | - | - | This study |
| 23 | HL2094 | F | 3 | 8 | No | No | c.5824T>A | p.Y1942N | ZP | Mid | Moderate | 32.0 | Likely pathogenic | PM1, PM2, PP1, PP3 | - | - | This study |
| 24 | HL0916 | F | 6 | 38 | No | No | c.5948C>T | p.T1983I | ZP | Mid | Mild | 33.0 | VUS | PM1, PM2, PP3 | - | - | This study |
| 25 | HL1026 | F | 0 | 4 | No | No | c.5987T>A | p.I1996N | ZP | Mid | Severe | 34.0 | Likely pathogenic | PM1, PM2, PP1, PP3 | - | - | This study |
| 26 | HL3056 | F | 4 | 32 | Yes | Yes | c.5999G>T | p.G2000V | ZP | Flat | Moderate | 26.2 | VUS | PM1, PM2, PP3 | - | - | This study |
| 27 | HL2846 | M | 2 | 71 | No | No | c.6183G>T | p.R2061S | Mid | Severe | 24.4 | VUS | PM2, PP1, PP3 | - | - | This study |