Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30995 | 93208;93209;93210 | chr2:178548643;178548642;178548641 | chr2:179413370;179413369;179413368 |
| N2AB | 29354 | 88285;88286;88287 | chr2:178548643;178548642;178548641 | chr2:179413370;179413369;179413368 |
| N2A | 28427 | 85504;85505;85506 | chr2:178548643;178548642;178548641 | chr2:179413370;179413369;179413368 |
| N2B | 21930 | 66013;66014;66015 | chr2:178548643;178548642;178548641 | chr2:179413370;179413369;179413368 |
| Novex-1 | 22055 | 66388;66389;66390 | chr2:178548643;178548642;178548641 | chr2:179413370;179413369;179413368 |
| Novex-2 | 22122 | 66589;66590;66591 | chr2:178548643;178548642;178548641 | chr2:179413370;179413369;179413368 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/N | rs886042408  |
-0.954 | 0.995 | N | 0.573 | 0.332 | 0.346085882481 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| T/N | rs886042408 |
-0.954 | 0.995 | N | 0.573 | 0.332 | 0.346085882481 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| T/N | rs886042408 |
-0.954 | 0.995 | N | 0.573 | 0.332 | 0.346085882481 | gnomAD-4.0.0 | 8.96709E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.67505E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1273 | likely_benign | 0.1266 | benign | -1.315 | Destabilizing | 0.64 | D | 0.541 | neutral | N | 0.480903621 | None | None | N |
| T/C | 0.3778 | ambiguous | 0.382 | ambiguous | -0.878 | Destabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | N |
| T/D | 0.6536 | likely_pathogenic | 0.657 | pathogenic | -0.842 | Destabilizing | 0.996 | D | 0.687 | prob.neutral | None | None | None | None | N |
| T/E | 0.4834 | ambiguous | 0.4904 | ambiguous | -0.664 | Destabilizing | 0.988 | D | 0.647 | neutral | None | None | None | None | N |
| T/F | 0.2579 | likely_benign | 0.2686 | benign | -1.18 | Destabilizing | 0.976 | D | 0.713 | prob.delet. | None | None | None | None | N |
| T/G | 0.4179 | ambiguous | 0.3994 | ambiguous | -1.701 | Destabilizing | 0.988 | D | 0.638 | neutral | None | None | None | None | N |
| T/H | 0.2861 | likely_benign | 0.2991 | benign | -1.772 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | N |
| T/I | 0.099 | likely_benign | 0.1112 | benign | -0.31 | Destabilizing | 0.811 | D | 0.555 | neutral | N | 0.503773134 | None | None | N |
| T/K | 0.3214 | likely_benign | 0.3417 | ambiguous | -0.275 | Destabilizing | 0.988 | D | 0.652 | neutral | None | None | None | None | N |
| T/L | 0.0992 | likely_benign | 0.104 | benign | -0.31 | Destabilizing | 0.034 | N | 0.377 | neutral | None | None | None | None | N |
| T/M | 0.0844 | likely_benign | 0.0904 | benign | -0.266 | Destabilizing | 0.976 | D | 0.69 | prob.neutral | None | None | None | None | N |
| T/N | 0.1856 | likely_benign | 0.1928 | benign | -0.829 | Destabilizing | 0.995 | D | 0.573 | neutral | N | 0.467927928 | None | None | N |
| T/P | 0.8309 | likely_pathogenic | 0.8174 | pathogenic | -0.615 | Destabilizing | 0.995 | D | 0.69 | prob.neutral | N | 0.500275324 | None | None | N |
| T/Q | 0.283 | likely_benign | 0.2888 | benign | -0.696 | Destabilizing | 0.996 | D | 0.695 | prob.neutral | None | None | None | None | N |
| T/R | 0.2492 | likely_benign | 0.2685 | benign | -0.457 | Destabilizing | 0.988 | D | 0.689 | prob.neutral | None | None | None | None | N |
| T/S | 0.1396 | likely_benign | 0.1401 | benign | -1.207 | Destabilizing | 0.946 | D | 0.521 | neutral | N | 0.455188816 | None | None | N |
| T/V | 0.0936 | likely_benign | 0.1048 | benign | -0.615 | Destabilizing | 0.015 | N | 0.261 | neutral | None | None | None | None | N |
| T/W | 0.6902 | likely_pathogenic | 0.6979 | pathogenic | -1.163 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | N |
| T/Y | 0.3247 | likely_benign | 0.3413 | ambiguous | -0.819 | Destabilizing | 0.988 | D | 0.731 | prob.delet. | None | None | 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.