Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21712 | 65359;65360;65361 | chr2:178584417;178584416;178584415 | chr2:179449144;179449143;179449142 |
| N2AB | 20071 | 60436;60437;60438 | chr2:178584417;178584416;178584415 | chr2:179449144;179449143;179449142 |
| N2A | 19144 | 57655;57656;57657 | chr2:178584417;178584416;178584415 | chr2:179449144;179449143;179449142 |
| N2B | 12647 | 38164;38165;38166 | chr2:178584417;178584416;178584415 | chr2:179449144;179449143;179449142 |
| Novex-1 | 12772 | 38539;38540;38541 | chr2:178584417;178584416;178584415 | chr2:179449144;179449143;179449142 |
| Novex-2 | 12839 | 38740;38741;38742 | chr2:178584417;178584416;178584415 | chr2:179449144;179449143;179449142 |
| 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/A | rs1278321308  |
0.014 | None | N | 0.077 | 0.06 | 0.0716867268079 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66003E-04 |
| T/A | rs1278321308 |
0.014 | None | N | 0.077 | 0.06 | 0.0716867268079 | gnomAD-4.0.0 | 1.59226E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43328E-05 | 0 |
| T/N | rs767459998 |
0.185 | 0.062 | N | 0.214 | 0.197 | 0.204665344411 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| T/N | rs767459998 |
0.185 | 0.062 | N | 0.214 | 0.197 | 0.204665344411 | gnomAD-4.0.0 | 1.59227E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86008E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0839 | likely_benign | 0.0734 | benign | -0.228 | Destabilizing | None | N | 0.077 | neutral | N | 0.498589106 | None | None | I |
| T/C | 0.3682 | ambiguous | 0.2823 | benign | -0.247 | Destabilizing | 0.824 | D | 0.249 | neutral | None | None | None | None | I |
| T/D | 0.5456 | ambiguous | 0.4343 | ambiguous | 0.138 | Stabilizing | 0.149 | N | 0.322 | neutral | None | None | None | None | I |
| T/E | 0.4925 | ambiguous | 0.3852 | ambiguous | 0.057 | Stabilizing | 0.149 | N | 0.263 | neutral | None | None | None | None | I |
| T/F | 0.2823 | likely_benign | 0.207 | benign | -0.809 | Destabilizing | 0.555 | D | 0.344 | neutral | None | None | None | None | I |
| T/G | 0.2267 | likely_benign | 0.1813 | benign | -0.328 | Destabilizing | 0.035 | N | 0.254 | neutral | None | None | None | None | I |
| T/H | 0.29 | likely_benign | 0.2335 | benign | -0.525 | Destabilizing | 0.824 | D | 0.299 | neutral | None | None | None | None | I |
| T/I | 0.1805 | likely_benign | 0.1427 | benign | -0.088 | Destabilizing | 0.062 | N | 0.256 | neutral | N | 0.484870447 | None | None | I |
| T/K | 0.3454 | ambiguous | 0.2759 | benign | -0.278 | Destabilizing | 0.081 | N | 0.257 | neutral | None | None | None | None | I |
| T/L | 0.1213 | likely_benign | 0.1003 | benign | -0.088 | Destabilizing | 0.035 | N | 0.242 | neutral | None | None | None | None | I |
| T/M | 0.106 | likely_benign | 0.0941 | benign | -0.074 | Destabilizing | 0.555 | D | 0.246 | neutral | None | None | None | None | I |
| T/N | 0.1277 | likely_benign | 0.1104 | benign | -0.052 | Destabilizing | 0.062 | N | 0.214 | neutral | N | 0.499663755 | None | None | I |
| T/P | 0.397 | ambiguous | 0.354 | ambiguous | -0.108 | Destabilizing | 0.317 | N | 0.305 | neutral | N | 0.475006543 | None | None | I |
| T/Q | 0.2877 | likely_benign | 0.2405 | benign | -0.253 | Destabilizing | 0.38 | N | 0.281 | neutral | None | None | None | None | I |
| T/R | 0.3052 | likely_benign | 0.2416 | benign | 0.01 | Stabilizing | 0.38 | N | 0.289 | neutral | None | None | None | None | I |
| T/S | 0.103 | likely_benign | 0.0933 | benign | -0.23 | Destabilizing | 0.001 | N | 0.093 | neutral | N | 0.436903142 | None | None | I |
| T/V | 0.1377 | likely_benign | 0.1077 | benign | -0.108 | Destabilizing | 0.002 | N | 0.119 | neutral | None | None | None | None | I |
| T/W | 0.6965 | likely_pathogenic | 0.6044 | pathogenic | -0.875 | Destabilizing | 0.935 | D | 0.342 | neutral | None | None | None | None | I |
| T/Y | 0.3234 | likely_benign | 0.2463 | benign | -0.562 | Destabilizing | 0.555 | D | 0.321 | neutral | None | None | 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.