Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30534 | 91825;91826;91827 | chr2:178550238;178550237;178550236 | chr2:179414965;179414964;179414963 |
| N2AB | 28893 | 86902;86903;86904 | chr2:178550238;178550237;178550236 | chr2:179414965;179414964;179414963 |
| N2A | 27966 | 84121;84122;84123 | chr2:178550238;178550237;178550236 | chr2:179414965;179414964;179414963 |
| N2B | 21469 | 64630;64631;64632 | chr2:178550238;178550237;178550236 | chr2:179414965;179414964;179414963 |
| Novex-1 | 21594 | 65005;65006;65007 | chr2:178550238;178550237;178550236 | chr2:179414965;179414964;179414963 |
| Novex-2 | 21661 | 65206;65207;65208 | chr2:178550238;178550237;178550236 | chr2:179414965;179414964;179414963 |
| 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/V | rs182549226  |
0.55 | 0.991 | N | 0.702 | 0.471 | None | gnomAD-2.1.1 | 8.08552E-04 | None | None | None | None | I | None | 0 | 1.69875E-04 | None | 0 | 0 | None | 3.26947E-04 | None | 2.45E-03 | 1.10465E-03 | 1.12644E-03 |
| D/V | rs182549226 |
0.55 | 0.991 | N | 0.702 | 0.471 | None | gnomAD-3.1.2 | 6.37713E-04 | None | None | None | None | I | None | 1.93143E-04 | 6.55E-05 | 0 | 0 | 0 | None | 1.78908E-03 | 0 | 9.55433E-04 | 6.22407E-04 | 4.79386E-04 |
| D/V | rs182549226 |
0.55 | 0.991 | N | 0.702 | 0.471 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 1E-03 | None |
| D/V | rs182549226 |
0.55 | 0.991 | N | 0.702 | 0.471 | None | gnomAD-4.0.0 | 9.38475E-04 | None | None | None | None | I | None | 1.46718E-04 | 1.66728E-04 | None | 0 | 0 | None | 3.3348E-03 | 1.65125E-04 | 1.02922E-03 | 4.06415E-04 | 4.48244E-04 |
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 | 0.1482 | likely_benign | 0.2058 | benign | 0.058 | Stabilizing | 0.939 | D | 0.565 | neutral | N | 0.490308501 | None | None | I |
| D/C | 0.537 | ambiguous | 0.672 | pathogenic | -0.305 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | I |
| D/E | 0.1072 | likely_benign | 0.1256 | benign | -0.506 | Destabilizing | 0.02 | N | 0.299 | neutral | N | 0.513510991 | None | None | I |
| D/F | 0.5869 | likely_pathogenic | 0.746 | pathogenic | -0.105 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | I |
| D/G | 0.1288 | likely_benign | 0.1827 | benign | -0.006 | Destabilizing | 0.939 | D | 0.613 | neutral | N | 0.497398846 | None | None | I |
| D/H | 0.2094 | likely_benign | 0.2816 | benign | 0.568 | Stabilizing | 0.998 | D | 0.641 | neutral | D | 0.527366385 | None | None | I |
| D/I | 0.383 | ambiguous | 0.52 | ambiguous | 0.156 | Stabilizing | 0.993 | D | 0.713 | prob.delet. | None | None | None | None | I |
| D/K | 0.2544 | likely_benign | 0.3302 | benign | 0.269 | Stabilizing | 0.91 | D | 0.613 | neutral | None | None | None | None | I |
| D/L | 0.3645 | ambiguous | 0.4772 | ambiguous | 0.156 | Stabilizing | 0.986 | D | 0.71 | prob.delet. | None | None | None | None | I |
| D/M | 0.5593 | ambiguous | 0.6903 | pathogenic | -0.094 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | I |
| D/N | 0.0886 | likely_benign | 0.1087 | benign | 0.094 | Stabilizing | 0.939 | D | 0.59 | neutral | D | 0.524346847 | None | None | I |
| D/P | 0.4402 | ambiguous | 0.5987 | pathogenic | 0.139 | Stabilizing | 0.993 | D | 0.657 | neutral | None | None | None | None | I |
| D/Q | 0.2195 | likely_benign | 0.2745 | benign | 0.077 | Stabilizing | 0.973 | D | 0.593 | neutral | None | None | None | None | I |
| D/R | 0.2798 | likely_benign | 0.3708 | ambiguous | 0.468 | Stabilizing | 0.986 | D | 0.679 | prob.neutral | None | None | None | None | I |
| D/S | 0.0923 | likely_benign | 0.1194 | benign | 0.003 | Stabilizing | 0.953 | D | 0.586 | neutral | None | None | None | None | I |
| D/T | 0.192 | likely_benign | 0.2598 | benign | 0.064 | Stabilizing | 0.986 | D | 0.591 | neutral | None | None | None | None | I |
| D/V | 0.2379 | likely_benign | 0.329 | benign | 0.139 | Stabilizing | 0.991 | D | 0.702 | prob.neutral | N | 0.516263569 | None | None | I |
| D/W | 0.8157 | likely_pathogenic | 0.8947 | pathogenic | -0.113 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | I |
| D/Y | 0.2479 | likely_benign | 0.346 | ambiguous | 0.097 | Stabilizing | 0.999 | D | 0.697 | prob.neutral | D | 0.527873364 | 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.