Table 2.
Variants reported by panel testing and WGS that may cause, or contribute to, cardiomyopathy
| HYPERTROPHIC CARDIOMYOPATHY TARGETED TEST RESULT | WGS RESULT | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| ID | Gene | DNA variant | Protein Variant | Classification | Gene | DNA variant | Protein Variant | Classification | ExAC allele frequency | Reported in other HCM probands? |
| 1 | MYBPC3 | c.2827C>T | p.Arg943X | P | Same | 1/16138 South Asian, 1/64974 European | Y | |||
| 2 | MYBPC3 | c.772G>A | p.Glu258Lys | P | Same | 3/43348 European | Y | |||
| 3 | MYBPC3 | c.3742_3759dup | p.Cys1253_Arg1254insGlyGlyIleTyrValCys | P | Variant ultimately identified and reported but initially missed by WGS | Absent | Y | |||
| 18 | MYBPC3 | c.772G>A | p.Glu258Lys | P | Same | 3/43348 European | Y | |||
| 19 | MYBPC3 | c.2905C>T | p.Gln969X | P | Same | Absent | Y | |||
| 21 | MYBPC3 | c.103C>T | p.Arg35Trp | VUS | Same | 3/50036 European | ||||
| 27 | MYBPC3 | c.927-9G>A | P | Same | Absent | Y | ||||
| 33 | MYBPC3 | c.2747G>A | p.Trp916X | P | Same | Absent | Y | |||
| 35 | MYBPC3 | c.3771C>A | p.Asn1257Lys | VUS | Same | Absent | Y | |||
| 26 | MYBPC3 | c.3005G>A | p.Arg1002Gln | VUS | Variant identified but did not meet MedSeq WGS reporting standards due to insufficient evidence for pathogenicity | 4/62092 European | Y | |||
| 6 | MYH7 | c.1987C>T | p.Arg663Cys | LP | Same | Absent | Y | |||
| 11 | MYH7 | c.4031G>A | p.Arg1344Gln | VUS | Same | Absent | Y | |||
| ILK | c.211del | p.Leu71CysfsX26 | VUS | Absent | N | |||||
| 15 | MYH7 | c.1357C>T | p.Arg453Cys | P | Same | Absent | Y | |||
| 22 | MYH7 | c.2717A>G | p.Asp906Gly | P | Same | Absent | Y | |||
| 38 | MYH7 | c.2609G>A | p.Arg870His | P | Same | 1/66732 European | Y | |||
| 34 | TNNI3 | c.568G>T | p.Asp190Tyr | LP | Same | Absent | Y | |||
| 41 | MYL2 | c.484G>A | p.Gly162Arg | LP | Same | Absent | Y | |||
| 31 | ACTN2 | c.1839+5G>C | VUS | Same | Absent | N | ||||
| 5 | ABCC9 | c.1982G>A | p.Arg661His | VUS | Same | 1/11498 Latino, 1/66718 European | N | |||
| FLNC | c.2450T>C | p.Ile817Thr | VUS | 1/9640 African, 1/16472 South Asian, 1/65918 European | N | |||||
| 37 | ABCC9 | c.2238-1G>A | VUS | Variant identified but did not meet MedSeq WGS reporting standards due to insufficient evidence for pathogenicity | 118/16384 South Asian, 70/9748 European, 1/9748 African | N | ||||
| 4 | No variant identified* | PTPN11 | c.1403C>T | p.Thr468Met | Pathogenic | 1/6614 European | N | |||
WGS indicates whole genome sequencing; P, Pathogenic; LP, likely pathogenic; MYBPC3, Myosin binding protein C; MYH7, Cardiac β-myosin heavy chain; TNNI3, Troponin I; MYL2, Myosin Light Chain 2; ACTN2, Actinin Alpha 2; ABCC9, ATP Binding Cassette Subfamily C Member 9; ILK, integrin-linked kinase; FLNC, Filamin-C; PTPN11, Protein Tyrosine Phosphatase, Non-Receptor Type 11
*
targeted genetic testing panel did not include PTPN11