Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33007 | 99244;99245;99246 | chr2:178538810;178538809;178538808 | chr2:179403537;179403536;179403535 |
| N2AB | 31366 | 94321;94322;94323 | chr2:178538810;178538809;178538808 | chr2:179403537;179403536;179403535 |
| N2A | 30439 | 91540;91541;91542 | chr2:178538810;178538809;178538808 | chr2:179403537;179403536;179403535 |
| N2B | 23942 | 72049;72050;72051 | chr2:178538810;178538809;178538808 | chr2:179403537;179403536;179403535 |
| Novex-1 | 24067 | 72424;72425;72426 | chr2:178538810;178538809;178538808 | chr2:179403537;179403536;179403535 |
| Novex-2 | 24134 | 72625;72626;72627 | chr2:178538810;178538809;178538808 | chr2:179403537;179403536;179403535 |
| 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/S | rs745893362  |
-1.523 | 0.998 | N | 0.713 | 0.463 | 0.8419198172 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | I | None | 2.58866E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/S | rs745893362 |
-1.523 | 0.998 | N | 0.713 | 0.463 | 0.8419198172 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/S | rs745893362 |
-1.523 | 0.998 | N | 0.713 | 0.463 | 0.8419198172 | gnomAD-4.0.0 | 2.62684E-05 | None | None | None | None | I | None | 9.62371E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5477 | ambiguous | 0.5932 | pathogenic | -1.826 | Destabilizing | 0.992 | D | 0.585 | neutral | None | None | None | None | I |
| I/C | 0.7304 | likely_pathogenic | 0.7464 | pathogenic | -1.405 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| I/D | 0.8764 | likely_pathogenic | 0.9115 | pathogenic | -1.092 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| I/E | 0.8079 | likely_pathogenic | 0.8532 | pathogenic | -1.023 | Destabilizing | 1.0 | D | 0.779 | deleterious | None | None | None | None | I |
| I/F | 0.1963 | likely_benign | 0.2256 | benign | -1.07 | Destabilizing | 0.998 | D | 0.597 | neutral | N | 0.471164521 | None | None | I |
| I/G | 0.8221 | likely_pathogenic | 0.8724 | pathogenic | -2.219 | Highly Destabilizing | 1.0 | D | 0.762 | deleterious | None | None | None | None | I |
| I/H | 0.7686 | likely_pathogenic | 0.8178 | pathogenic | -1.249 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | I |
| I/K | 0.7014 | likely_pathogenic | 0.7614 | pathogenic | -1.403 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| I/L | 0.1479 | likely_benign | 0.1631 | benign | -0.788 | Destabilizing | 0.889 | D | 0.376 | neutral | N | 0.501471909 | None | None | I |
| I/M | 0.1318 | likely_benign | 0.1476 | benign | -0.776 | Destabilizing | 0.998 | D | 0.604 | neutral | N | 0.484348159 | None | None | I |
| I/N | 0.4572 | ambiguous | 0.5316 | ambiguous | -1.368 | Destabilizing | 0.999 | D | 0.786 | deleterious | N | 0.509960832 | None | None | I |
| I/P | 0.7598 | likely_pathogenic | 0.7725 | pathogenic | -1.104 | Destabilizing | 1.0 | D | 0.787 | deleterious | None | None | None | None | I |
| I/Q | 0.717 | likely_pathogenic | 0.7797 | pathogenic | -1.423 | Destabilizing | 1.0 | D | 0.781 | deleterious | None | None | None | None | I |
| I/R | 0.6354 | likely_pathogenic | 0.721 | pathogenic | -0.868 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| I/S | 0.5424 | ambiguous | 0.6158 | pathogenic | -2.086 | Highly Destabilizing | 0.998 | D | 0.713 | prob.delet. | N | 0.468218914 | None | None | I |
| I/T | 0.4405 | ambiguous | 0.467 | ambiguous | -1.876 | Destabilizing | 0.989 | D | 0.663 | neutral | N | 0.488716252 | None | None | I |
| I/V | 0.0941 | likely_benign | 0.0901 | benign | -1.104 | Destabilizing | 0.333 | N | 0.199 | neutral | N | 0.40686545 | None | None | I |
| I/W | 0.8519 | likely_pathogenic | 0.8966 | pathogenic | -1.136 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | I |
| I/Y | 0.5734 | likely_pathogenic | 0.643 | pathogenic | -0.936 | Destabilizing | 1.0 | D | 0.705 | prob.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.