Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30055 | 90388;90389;90390 | chr2:178552737;178552736;178552735 | chr2:179417464;179417463;179417462 |
| N2AB | 28414 | 85465;85466;85467 | chr2:178552737;178552736;178552735 | chr2:179417464;179417463;179417462 |
| N2A | 27487 | 82684;82685;82686 | chr2:178552737;178552736;178552735 | chr2:179417464;179417463;179417462 |
| N2B | 20990 | 63193;63194;63195 | chr2:178552737;178552736;178552735 | chr2:179417464;179417463;179417462 |
| Novex-1 | 21115 | 63568;63569;63570 | chr2:178552737;178552736;178552735 | chr2:179417464;179417463;179417462 |
| Novex-2 | 21182 | 63769;63770;63771 | chr2:178552737;178552736;178552735 | chr2:179417464;179417463;179417462 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs878879065  |
None | 0.993 | N | 0.663 | 0.327 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs878879065 |
None | 0.993 | N | 0.663 | 0.327 | None | gnomAD-4.0.0 | 6.57047E-06 | None | None | None | None | I | None | 2.41196E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/V | rs759806991 |
0.283 | 0.997 | N | 0.713 | 0.459 | 0.472344434578 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| D/V | rs759806991 |
0.283 | 0.997 | N | 0.713 | 0.459 | 0.472344434578 | gnomAD-4.0.0 | 4.78917E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.55896E-05 | None | 0 | 0 | 2.69829E-06 | 0 | 1.6564E-05 |
| D/Y | None | None | 1.0 | N | 0.715 | 0.346 | 0.600342123009 | gnomAD-4.0.0 | 1.59106E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77346E-05 | None | 0 | 0 | 0 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2112 | likely_benign | 0.2002 | benign | -0.225 | Destabilizing | 0.993 | D | 0.589 | neutral | N | 0.425453997 | None | None | I |
| D/C | 0.7738 | likely_pathogenic | 0.7508 | pathogenic | 0.016 | Stabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| D/E | 0.1835 | likely_benign | 0.1868 | benign | -0.336 | Destabilizing | 0.117 | N | 0.265 | neutral | N | 0.387493042 | None | None | I |
| D/F | 0.7303 | likely_pathogenic | 0.6933 | pathogenic | -0.187 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| D/G | 0.3236 | likely_benign | 0.2982 | benign | -0.417 | Destabilizing | 0.977 | D | 0.623 | neutral | N | 0.445773342 | None | None | I |
| D/H | 0.4659 | ambiguous | 0.4362 | ambiguous | -0.022 | Destabilizing | 0.999 | D | 0.68 | prob.neutral | N | 0.505032289 | None | None | I |
| D/I | 0.3996 | ambiguous | 0.3738 | ambiguous | 0.228 | Stabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | I |
| D/K | 0.5831 | likely_pathogenic | 0.5709 | pathogenic | 0.306 | Stabilizing | 0.99 | D | 0.639 | neutral | None | None | None | None | I |
| D/L | 0.4455 | ambiguous | 0.4245 | ambiguous | 0.228 | Stabilizing | 0.995 | D | 0.711 | prob.delet. | None | None | None | None | I |
| D/M | 0.7013 | likely_pathogenic | 0.6806 | pathogenic | 0.299 | Stabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | I |
| D/N | 0.1543 | likely_benign | 0.1445 | benign | 0.046 | Stabilizing | 0.993 | D | 0.663 | neutral | N | 0.497951601 | None | None | I |
| D/P | 0.7051 | likely_pathogenic | 0.7122 | pathogenic | 0.099 | Stabilizing | 0.998 | D | 0.682 | prob.neutral | None | None | None | None | I |
| D/Q | 0.4901 | ambiguous | 0.4768 | ambiguous | 0.065 | Stabilizing | 0.99 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/R | 0.6197 | likely_pathogenic | 0.5966 | pathogenic | 0.472 | Stabilizing | 0.995 | D | 0.699 | prob.neutral | None | None | None | None | I |
| D/S | 0.182 | likely_benign | 0.1747 | benign | -0.062 | Destabilizing | 0.983 | D | 0.629 | neutral | None | None | None | None | I |
| D/T | 0.3455 | ambiguous | 0.3245 | benign | 0.083 | Stabilizing | 0.995 | D | 0.692 | prob.neutral | None | None | None | None | I |
| D/V | 0.2423 | likely_benign | 0.2262 | benign | 0.099 | Stabilizing | 0.997 | D | 0.713 | prob.delet. | N | 0.467860767 | None | None | I |
| D/W | 0.941 | likely_pathogenic | 0.9297 | pathogenic | -0.071 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | I |
| D/Y | 0.3522 | ambiguous | 0.3165 | benign | 0.049 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.468432723 | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.