Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26609 | 80050;80051;80052 | chr2:178566307;178566306;178566305 | chr2:179431034;179431033;179431032 |
| N2AB | 24968 | 75127;75128;75129 | chr2:178566307;178566306;178566305 | chr2:179431034;179431033;179431032 |
| N2A | 24041 | 72346;72347;72348 | chr2:178566307;178566306;178566305 | chr2:179431034;179431033;179431032 |
| N2B | 17544 | 52855;52856;52857 | chr2:178566307;178566306;178566305 | chr2:179431034;179431033;179431032 |
| Novex-1 | 17669 | 53230;53231;53232 | chr2:178566307;178566306;178566305 | chr2:179431034;179431033;179431032 |
| Novex-2 | 17736 | 53431;53432;53433 | chr2:178566307;178566306;178566305 | chr2:179431034;179431033;179431032 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs771678075  |
-0.227 | 0.997 | N | 0.576 | 0.401 | 0.404315859256 | 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 |
| S/C | rs771678075 |
-0.227 | 0.997 | N | 0.576 | 0.401 | 0.404315859256 | gnomAD-4.0.0 | 1.59151E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85878E-06 | 0 | 0 |
| S/T | rs1328705248 |
-0.277 | 0.014 | N | 0.22 | 0.166 | 0.117506650769 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/T | rs1328705248 |
-0.277 | 0.014 | N | 0.22 | 0.166 | 0.117506650769 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | rs1328705248 |
-0.277 | 0.014 | N | 0.22 | 0.166 | 0.117506650769 | gnomAD-4.0.0 | 6.57488E-06 | None | None | None | None | N | None | 2.41289E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1161 | likely_benign | 0.1058 | benign | -0.517 | Destabilizing | 0.489 | N | 0.503 | neutral | N | 0.456238773 | None | None | N |
| S/C | 0.1308 | likely_benign | 0.1189 | benign | -0.314 | Destabilizing | 0.997 | D | 0.576 | neutral | N | 0.480636905 | None | None | N |
| S/D | 0.7104 | likely_pathogenic | 0.6685 | pathogenic | -0.231 | Destabilizing | 0.754 | D | 0.442 | neutral | None | None | None | None | N |
| S/E | 0.7992 | likely_pathogenic | 0.7594 | pathogenic | -0.319 | Destabilizing | 0.86 | D | 0.438 | neutral | None | None | None | None | N |
| S/F | 0.319 | likely_benign | 0.2436 | benign | -1.083 | Destabilizing | 0.97 | D | 0.657 | neutral | N | 0.487131365 | None | None | N |
| S/G | 0.1416 | likely_benign | 0.1386 | benign | -0.641 | Destabilizing | 0.754 | D | 0.481 | neutral | None | None | None | None | N |
| S/H | 0.5008 | ambiguous | 0.4279 | ambiguous | -1.212 | Destabilizing | 0.994 | D | 0.565 | neutral | None | None | None | None | N |
| S/I | 0.2335 | likely_benign | 0.2164 | benign | -0.313 | Destabilizing | 0.956 | D | 0.645 | neutral | None | None | None | None | N |
| S/K | 0.844 | likely_pathogenic | 0.8194 | pathogenic | -0.555 | Destabilizing | 0.86 | D | 0.444 | neutral | None | None | None | None | N |
| S/L | 0.154 | likely_benign | 0.1368 | benign | -0.313 | Destabilizing | 0.754 | D | 0.507 | neutral | None | None | None | None | N |
| S/M | 0.2407 | likely_benign | 0.2309 | benign | 0.13 | Stabilizing | 0.998 | D | 0.553 | neutral | None | None | None | None | N |
| S/N | 0.1856 | likely_benign | 0.1826 | benign | -0.304 | Destabilizing | 0.019 | N | 0.261 | neutral | None | None | None | None | N |
| S/P | 0.4268 | ambiguous | 0.3713 | ambiguous | -0.353 | Destabilizing | 0.97 | D | 0.537 | neutral | N | 0.483203074 | None | None | N |
| S/Q | 0.6615 | likely_pathogenic | 0.6224 | pathogenic | -0.644 | Destabilizing | 0.978 | D | 0.503 | neutral | None | None | None | None | N |
| S/R | 0.8025 | likely_pathogenic | 0.7679 | pathogenic | -0.293 | Destabilizing | 0.956 | D | 0.537 | neutral | None | None | None | None | N |
| S/T | 0.0928 | likely_benign | 0.087 | benign | -0.399 | Destabilizing | 0.014 | N | 0.22 | neutral | N | 0.402355346 | None | None | N |
| S/V | 0.2252 | likely_benign | 0.2101 | benign | -0.353 | Destabilizing | 0.915 | D | 0.542 | neutral | None | None | None | None | N |
| S/W | 0.5477 | ambiguous | 0.4879 | ambiguous | -1.038 | Destabilizing | 0.998 | D | 0.707 | prob.neutral | None | None | None | None | N |
| S/Y | 0.3244 | likely_benign | 0.2522 | benign | -0.775 | Destabilizing | 0.99 | D | 0.649 | neutral | N | 0.498487671 | 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.