Table 2.
Likely pathogenic, pathogenic and highly suspicious variants of uncertain significance identified.
| Gene | gnomAD count | Variant consequence | DNA/protein alteration | Missense constraint score (z) | pLI | ClinVar | ACMG prediction | Patient |
|---|---|---|---|---|---|---|---|---|
| Likely pathogenic/pathogenic variants in nuclear genes | ||||||||
| NKX2-5 | 0 | SNV (stop gained) | NM_004387.3:c.744 C > A/ NP_004378.1:p.Tyr248Ter | 1.84 | 0.86 | NR | Pathogenic (PVS1, PM2, PP3) | BHS |
| 0 | INDEL (frameshift) | NM_004387.3:c.677_680del/ NP_004378.1:p.Asp226AlafsTer5 | NR | Likely pathogenic (PVS1, PM2) | CBT | |||
| TBX5 | 0 | INDEL (Frameshift) | NM_000192.3:c.105dup/ NP_000183.2:p.Ser36GlnfsTer25 | 1.63 | 0.99 | NR | Pathogenic (PVS1, PM2, PP3) | BRP |
| Highly suspicious variants of uncertain significance in nuclear genes | ||||||||
| ACTC1 | 0 | Missense (possible splice) | NM_005159.4:c.723 C > G/ NP_005150.1:p.Ser241Arg | 5.25 | 0.95 | NR | VUS (PM2, PP2, PP3) | BLM |
| DSP | 0 | INDEL | NM_001008844.1:c.2598_2603del/ NP_001008844.1:p.Trp867_Gln868del | 0.91 | 1 | NR | VUS (PM2) | SS |
| HCN4 | 0 | SNV (missense) | NM_005477.2:c.1438 G > A/ NP_005468.1:p.Gly480Ser | 4.83 | 0.23 | NR | VUS (PM2, PP3) | ME |
| MYBPC 3 | 0 | SNV (missense) | NM_000256.3:c.989 C > T/ NP_000247.2:p.Pro330Leu | 0.69 | 0 | NR | VUS (PM1, PM2, PP3) | BLU |
| MYH6 | 4 | SNV (missense) | NM_002471.3:c.756 C > G/ NP_002462.2:p.His252Gln | 2.87 | 0 | 537949 | VUS (PP3) | BSQ |
| PRDM16 | 0 | INDEL (frameshift) | NM_022114.3:c.564del/ NP_071397.3:p.Ser189ValfsTer22 | 2.06 | 1 | NR | VUS (PM2, PP3) | ALW |
| TBX5 | 0 | Intron (splice region) | NM_000192.3:c.510 + 5 G > T/- | 1.63 | 0.99 | NR | VUS (PM2, PP3) | BEW |
| TPM1 | 0 | SNV (missense) | NM_000366.5:c.647 A > G/ NP_000357.3:p.Gln216Arg | 3.42 | 0.8 | NR | VUS (PM2, PP2, PP3) | AXT |
| Highly suspicious variants of uncertain significance in mitochondrial genes | ||||||||
| MT-TV | N/A | SNV | c.1612C > T | – | – | – | – | BKS |
SNV single nucleotide variant, INDEL insertion-deletion, NR not reported, VUS variant of uncertain significance. Positive missense constraint scores (z) indicate that less variants are observed in the particular gene than expected. pLi probability of loss of function intolerance. pLi scores close to 1 indicate that a gene cannot tolerate protein-truncating variation. ACMG American College of Medical Genetics.