Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23190 | 69793;69794;69795 | chr2:178576676;178576675;178576674 | chr2:179441403;179441402;179441401 |
| N2AB | 21549 | 64870;64871;64872 | chr2:178576676;178576675;178576674 | chr2:179441403;179441402;179441401 |
| N2A | 20622 | 62089;62090;62091 | chr2:178576676;178576675;178576674 | chr2:179441403;179441402;179441401 |
| N2B | 14125 | 42598;42599;42600 | chr2:178576676;178576675;178576674 | chr2:179441403;179441402;179441401 |
| Novex-1 | 14250 | 42973;42974;42975 | chr2:178576676;178576675;178576674 | chr2:179441403;179441402;179441401 |
| Novex-2 | 14317 | 43174;43175;43176 | chr2:178576676;178576675;178576674 | chr2:179441403;179441402;179441401 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/M | None | None | 0.196 | N | 0.399 | 0.068 | 0.144782658237 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | rs762698812  |
None | 0.001 | N | 0.241 | 0.081 | 0.347659731818 | gnomAD-4.0.0 | 3.18321E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85925E-06 | 0 | 3.02517E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1263 | likely_benign | 0.132 | benign | -1.296 | Destabilizing | 0.001 | N | 0.197 | neutral | None | None | None | None | N |
| I/C | 0.397 | ambiguous | 0.4169 | ambiguous | -0.799 | Destabilizing | 0.245 | N | 0.374 | neutral | None | None | None | None | N |
| I/D | 0.5033 | ambiguous | 0.5525 | ambiguous | -0.632 | Destabilizing | 0.008 | N | 0.366 | neutral | None | None | None | None | N |
| I/E | 0.4578 | ambiguous | 0.4862 | ambiguous | -0.675 | Destabilizing | 0.008 | N | 0.347 | neutral | None | None | None | None | N |
| I/F | 0.1613 | likely_benign | 0.1544 | benign | -0.998 | Destabilizing | 0.085 | N | 0.346 | neutral | None | None | None | None | N |
| I/G | 0.2499 | likely_benign | 0.2693 | benign | -1.563 | Destabilizing | 0.002 | N | 0.35 | neutral | None | None | None | None | N |
| I/H | 0.3417 | ambiguous | 0.3504 | ambiguous | -0.822 | Destabilizing | None | N | 0.329 | neutral | None | None | None | None | N |
| I/K | 0.2722 | likely_benign | 0.2835 | benign | -0.838 | Destabilizing | 0.006 | N | 0.367 | neutral | N | 0.462164159 | None | None | N |
| I/L | 0.0819 | likely_benign | 0.0823 | benign | -0.669 | Destabilizing | 0.001 | N | 0.231 | neutral | N | 0.434478912 | None | None | N |
| I/M | 0.0778 | likely_benign | 0.0762 | benign | -0.528 | Destabilizing | 0.196 | N | 0.399 | neutral | N | 0.471997151 | None | None | N |
| I/N | 0.0927 | likely_benign | 0.1013 | benign | -0.561 | Destabilizing | 0.008 | N | 0.363 | neutral | None | None | None | None | N |
| I/P | 0.5931 | likely_pathogenic | 0.6817 | pathogenic | -0.845 | Destabilizing | 0.037 | N | 0.422 | neutral | None | None | None | None | N |
| I/Q | 0.2611 | likely_benign | 0.2708 | benign | -0.774 | Destabilizing | 0.037 | N | 0.429 | neutral | None | None | None | None | N |
| I/R | 0.2129 | likely_benign | 0.2304 | benign | -0.253 | Destabilizing | 0.014 | N | 0.423 | neutral | N | 0.474554666 | None | None | N |
| I/S | 0.0941 | likely_benign | 0.1013 | benign | -1.124 | Destabilizing | None | N | 0.187 | neutral | None | None | None | None | N |
| I/T | 0.0764 | likely_benign | 0.0734 | benign | -1.051 | Destabilizing | None | N | 0.135 | neutral | N | 0.406212089 | None | None | N |
| I/V | 0.061 | likely_benign | 0.0612 | benign | -0.845 | Destabilizing | 0.001 | N | 0.241 | neutral | N | 0.391477497 | None | None | N |
| I/W | 0.6955 | likely_pathogenic | 0.7091 | pathogenic | -1.016 | Destabilizing | 0.497 | N | 0.435 | neutral | None | None | None | None | N |
| I/Y | 0.4166 | ambiguous | 0.4282 | ambiguous | -0.8 | Destabilizing | 0.044 | N | 0.431 | 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.