Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16111 | 48556;48557;48558 | chr2:178615770;178615769;178615768 | chr2:179480497;179480496;179480495 |
| N2AB | 14470 | 43633;43634;43635 | chr2:178615770;178615769;178615768 | chr2:179480497;179480496;179480495 |
| N2A | 13543 | 40852;40853;40854 | chr2:178615770;178615769;178615768 | chr2:179480497;179480496;179480495 |
| N2B | 7046 | 21361;21362;21363 | chr2:178615770;178615769;178615768 | chr2:179480497;179480496;179480495 |
| Novex-1 | 7171 | 21736;21737;21738 | chr2:178615770;178615769;178615768 | chr2:179480497;179480496;179480495 |
| Novex-2 | 7238 | 21937;21938;21939 | chr2:178615770;178615769;178615768 | chr2:179480497;179480496;179480495 |
| 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/E | None | None | 0.014 | N | 0.251 | 0.058 | 0.0666544352282 | gnomAD-4.0.0 | 1.59582E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43575E-05 | 0 |
| D/N | rs769898196  |
-0.307 | 0.032 | N | 0.215 | 0.13 | 0.143124449307 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.74E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs769898196 |
-0.307 | 0.032 | N | 0.215 | 0.13 | 0.143124449307 | gnomAD-4.0.0 | 3.42542E-06 | None | None | None | None | N | None | 0 | 6.72706E-05 | None | 0 | 0 | None | 0 | 0 | 1.80062E-06 | 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 | 0.1924 | likely_benign | 0.2209 | benign | 0.075 | Stabilizing | 0.698 | D | 0.559 | neutral | N | 0.475808419 | None | None | N |
| D/C | 0.6908 | likely_pathogenic | 0.7539 | pathogenic | -0.12 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/E | 0.1791 | likely_benign | 0.2177 | benign | -0.41 | Destabilizing | 0.014 | N | 0.251 | neutral | N | 0.470476329 | None | None | N |
| D/F | 0.7337 | likely_pathogenic | 0.7678 | pathogenic | 0.592 | Stabilizing | 0.998 | D | 0.674 | neutral | None | None | None | None | N |
| D/G | 0.1773 | likely_benign | 0.1992 | benign | -0.222 | Destabilizing | 0.698 | D | 0.589 | neutral | N | 0.472658178 | None | None | N |
| D/H | 0.3288 | likely_benign | 0.3847 | ambiguous | 0.844 | Stabilizing | 0.984 | D | 0.669 | neutral | N | 0.469750403 | None | None | N |
| D/I | 0.5719 | likely_pathogenic | 0.6136 | pathogenic | 0.835 | Stabilizing | 0.978 | D | 0.692 | prob.neutral | None | None | None | None | N |
| D/K | 0.3958 | ambiguous | 0.4466 | ambiguous | 0.381 | Stabilizing | 0.754 | D | 0.634 | neutral | None | None | None | None | N |
| D/L | 0.5169 | ambiguous | 0.5775 | pathogenic | 0.835 | Stabilizing | 0.956 | D | 0.693 | prob.neutral | None | None | None | None | N |
| D/M | 0.7041 | likely_pathogenic | 0.7581 | pathogenic | 0.71 | Stabilizing | 0.998 | D | 0.671 | neutral | None | None | None | None | N |
| D/N | 0.1134 | likely_benign | 0.1323 | benign | -0.31 | Destabilizing | 0.032 | N | 0.215 | neutral | N | 0.480702495 | None | None | N |
| D/P | 0.7987 | likely_pathogenic | 0.8215 | pathogenic | 0.607 | Stabilizing | 0.978 | D | 0.69 | prob.neutral | None | None | None | None | N |
| D/Q | 0.3638 | ambiguous | 0.4346 | ambiguous | -0.161 | Destabilizing | 0.915 | D | 0.618 | neutral | None | None | None | None | N |
| D/R | 0.4274 | ambiguous | 0.4755 | ambiguous | 0.716 | Stabilizing | 0.956 | D | 0.67 | neutral | None | None | None | None | N |
| D/S | 0.1304 | likely_benign | 0.149 | benign | -0.42 | Destabilizing | 0.754 | D | 0.495 | neutral | None | None | None | None | N |
| D/T | 0.3034 | likely_benign | 0.338 | benign | -0.153 | Destabilizing | 0.956 | D | 0.644 | neutral | None | None | None | None | N |
| D/V | 0.3372 | likely_benign | 0.3743 | ambiguous | 0.607 | Stabilizing | 0.942 | D | 0.694 | prob.neutral | N | 0.479028021 | None | None | N |
| D/W | 0.9271 | likely_pathogenic | 0.9404 | pathogenic | 0.769 | Stabilizing | 0.998 | D | 0.7 | prob.neutral | None | None | None | None | N |
| D/Y | 0.3604 | ambiguous | 0.3793 | ambiguous | 0.877 | Stabilizing | 0.997 | D | 0.671 | neutral | D | 0.524987518 | None | None | N |
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.