Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31175 | 93748;93749;93750 | chr2:178548103;178548102;178548101 | chr2:179412830;179412829;179412828 |
| N2AB | 29534 | 88825;88826;88827 | chr2:178548103;178548102;178548101 | chr2:179412830;179412829;179412828 |
| N2A | 28607 | 86044;86045;86046 | chr2:178548103;178548102;178548101 | chr2:179412830;179412829;179412828 |
| N2B | 22110 | 66553;66554;66555 | chr2:178548103;178548102;178548101 | chr2:179412830;179412829;179412828 |
| Novex-1 | 22235 | 66928;66929;66930 | chr2:178548103;178548102;178548101 | chr2:179412830;179412829;179412828 |
| Novex-2 | 22302 | 67129;67130;67131 | chr2:178548103;178548102;178548101 | chr2:179412830;179412829;179412828 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs766346925  |
-0.212 | 0.983 | N | 0.395 | 0.245 | None | gnomAD-2.1.1 | 8.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 8.87E-06 | 0 |
| R/C | rs766346925 |
-0.212 | 0.983 | N | 0.395 | 0.245 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/C | rs766346925 |
-0.212 | 0.983 | N | 0.395 | 0.245 | None | gnomAD-4.0.0 | 3.7182E-06 | None | None | None | None | N | None | 1.3354E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54282E-06 | 1.09794E-05 | 1.60102E-05 |
| R/H | rs72648251 |
-0.521 | 0.002 | N | 0.257 | 0.105 | None | gnomAD-2.1.1 | 4.31563E-04 | None | None | None | None | N | None | 1.23998E-04 | 5.65E-05 | None | 0 | 2.04876E-04 | None | 3.27E-05 | None | 9.99121E-04 | 6.55339E-04 | 2.80505E-04 |
| R/H | rs72648251 |
-0.521 | 0.002 | N | 0.257 | 0.105 | None | gnomAD-3.1.2 | 2.95792E-04 | None | None | None | None | N | None | 2.41359E-04 | 0 | 0 | 0 | 0 | None | 1.88324E-04 | 0 | 4.85223E-04 | 0 | 0 |
| R/H | rs72648251 |
-0.521 | 0.002 | N | 0.257 | 0.105 | None | gnomAD-4.0.0 | 4.41832E-04 | None | None | None | None | N | None | 1.60209E-04 | 5.00067E-05 | None | 0 | 8.91186E-05 | None | 7.96626E-04 | 0 | 5.29754E-04 | 2.19563E-05 | 2.56189E-04 |
| R/S | rs766346925 |
-0.172 | 0.002 | N | 0.201 | 0.139 | 0.176091768786 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/S | rs766346925 |
-0.172 | 0.002 | N | 0.201 | 0.139 | 0.176091768786 | gnomAD-4.0.0 | 6.84181E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99455E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.1609 | likely_benign | 0.1357 | benign | 0.066 | Stabilizing | 0.015 | N | 0.271 | neutral | None | None | None | None | N |
| R/C | 0.1248 | likely_benign | 0.1057 | benign | -0.184 | Destabilizing | 0.983 | D | 0.395 | neutral | N | 0.513035697 | None | None | N |
| R/D | 0.1691 | likely_benign | 0.127 | benign | -0.212 | Destabilizing | 0.033 | N | 0.293 | neutral | None | None | None | None | N |
| R/E | 0.1628 | likely_benign | 0.1309 | benign | -0.157 | Destabilizing | 0.015 | N | 0.298 | neutral | None | None | None | None | N |
| R/F | 0.3637 | ambiguous | 0.3161 | benign | -0.198 | Destabilizing | 0.367 | N | 0.449 | neutral | None | None | None | None | N |
| R/G | 0.0632 | likely_benign | 0.0563 | benign | -0.104 | Destabilizing | None | N | 0.211 | neutral | N | 0.318819604 | None | None | N |
| R/H | 0.0671 | likely_benign | 0.0593 | benign | -0.609 | Destabilizing | 0.002 | N | 0.257 | neutral | N | 0.456315622 | None | None | N |
| R/I | 0.2528 | likely_benign | 0.2395 | benign | 0.472 | Stabilizing | 0.251 | N | 0.446 | neutral | None | None | None | None | N |
| R/K | 0.0728 | likely_benign | 0.0782 | benign | -0.084 | Destabilizing | 0.015 | N | 0.278 | neutral | None | None | None | None | N |
| R/L | 0.1666 | likely_benign | 0.148 | benign | 0.472 | Stabilizing | 0.116 | N | 0.318 | neutral | N | 0.49383386 | None | None | N |
| R/M | 0.1688 | likely_benign | 0.1768 | benign | -0.005 | Destabilizing | 0.54 | D | 0.395 | neutral | None | None | None | None | N |
| R/N | 0.1286 | likely_benign | 0.1055 | benign | 0.045 | Stabilizing | None | N | 0.199 | neutral | None | None | None | None | N |
| R/P | 0.4219 | ambiguous | 0.3586 | ambiguous | 0.357 | Stabilizing | 0.391 | N | 0.425 | neutral | N | 0.460164004 | None | None | N |
| R/Q | 0.0724 | likely_benign | 0.0686 | benign | -0.009 | Destabilizing | 0.001 | N | 0.232 | neutral | None | None | None | None | N |
| R/S | 0.1412 | likely_benign | 0.118 | benign | -0.193 | Destabilizing | 0.002 | N | 0.201 | neutral | N | 0.391168066 | None | None | N |
| R/T | 0.1223 | likely_benign | 0.1115 | benign | -0.016 | Destabilizing | 0.033 | N | 0.304 | neutral | None | None | None | None | N |
| R/V | 0.2685 | likely_benign | 0.2383 | benign | 0.357 | Stabilizing | 0.142 | N | 0.398 | neutral | None | None | None | None | N |
| R/W | 0.1687 | likely_benign | 0.1645 | benign | -0.332 | Destabilizing | 0.931 | D | 0.387 | neutral | None | None | None | None | N |
| R/Y | 0.2042 | likely_benign | 0.1684 | benign | 0.082 | Stabilizing | 0.076 | N | 0.433 | neutral | 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.