Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 5497 | 16714;16715;16716 | chr2:178732572;178732571;178732570 | chr2:179597299;179597298;179597297 |
| N2AB | 5180 | 15763;15764;15765 | chr2:178732572;178732571;178732570 | chr2:179597299;179597298;179597297 |
| N2A | 4253 | 12982;12983;12984 | chr2:178732572;178732571;178732570 | chr2:179597299;179597298;179597297 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/C | rs946624122  |
None | 1.0 | N | 0.697 | 0.361 | 0.611492100817 | gnomAD-4.0.0 | 4.78982E-06 | None | None | None | None | I | None | 2.98739E-05 | 0 | None | 0 | 2.52232E-05 | None | 0 | 0 | 3.59801E-06 | 0 | 1.65695E-05 |
| Y/H | rs1279249843 |
-0.236 | 0.998 | N | 0.575 | 0.3 | 0.386395597597 | 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 |
| Y/H | rs1279249843 |
-0.236 | 0.998 | N | 0.575 | 0.3 | 0.386395597597 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.77555E-04 |
| Y/H | rs1279249843 |
-0.236 | 0.998 | N | 0.575 | 0.3 | 0.386395597597 | gnomAD-4.0.0 | 3.84389E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78675E-06 | 0 | 2.84495E-05 |
| Y/N | rs1279249843 |
None | 0.998 | N | 0.693 | 0.458 | 0.634143885914 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 9.96E-05 | 0 | None | 0 | None | 0 | 0 | 0 |
| Y/N | rs1279249843 |
None | 0.998 | N | 0.693 | 0.458 | 0.634143885914 | gnomAD-4.0.0 | 1.59155E-06 | None | None | None | None | I | None | 0 | 0 | None | 4.7669E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Y/A | 0.4081 | ambiguous | 0.4558 | ambiguous | -1.538 | Destabilizing | 0.985 | D | 0.555 | neutral | None | None | None | None | I |
| Y/C | 0.154 | likely_benign | 0.1588 | benign | -0.461 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.495135874 | None | None | I |
| Y/D | 0.2437 | likely_benign | 0.3254 | benign | 0.839 | Stabilizing | 0.998 | D | 0.701 | prob.neutral | N | 0.43645293 | None | None | I |
| Y/E | 0.5372 | ambiguous | 0.6396 | pathogenic | 0.89 | Stabilizing | 0.999 | D | 0.677 | prob.neutral | None | None | None | None | I |
| Y/F | 0.0822 | likely_benign | 0.0831 | benign | -0.65 | Destabilizing | 0.031 | N | 0.137 | neutral | N | 0.440725386 | None | None | I |
| Y/G | 0.4041 | ambiguous | 0.4725 | ambiguous | -1.805 | Destabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | I |
| Y/H | 0.1388 | likely_benign | 0.1611 | benign | -0.34 | Destabilizing | 0.998 | D | 0.575 | neutral | N | 0.40303379 | None | None | I |
| Y/I | 0.326 | likely_benign | 0.404 | ambiguous | -0.786 | Destabilizing | 0.97 | D | 0.554 | neutral | None | None | None | None | I |
| Y/K | 0.4628 | ambiguous | 0.5782 | pathogenic | -0.298 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| Y/L | 0.3688 | ambiguous | 0.4325 | ambiguous | -0.786 | Destabilizing | 0.871 | D | 0.537 | neutral | None | None | None | None | I |
| Y/M | 0.5443 | ambiguous | 0.6018 | pathogenic | -0.543 | Destabilizing | 0.999 | D | 0.655 | neutral | None | None | None | None | I |
| Y/N | 0.152 | likely_benign | 0.1865 | benign | -0.436 | Destabilizing | 0.998 | D | 0.693 | prob.neutral | N | 0.355239843 | None | None | I |
| Y/P | 0.8777 | likely_pathogenic | 0.9349 | pathogenic | -1.023 | Destabilizing | 0.999 | D | 0.711 | prob.delet. | None | None | None | None | I |
| Y/Q | 0.3758 | ambiguous | 0.4557 | ambiguous | -0.367 | Destabilizing | 0.999 | D | 0.65 | neutral | None | None | None | None | I |
| Y/R | 0.2797 | likely_benign | 0.3582 | ambiguous | 0.037 | Stabilizing | 0.999 | D | 0.695 | prob.neutral | None | None | None | None | I |
| Y/S | 0.1653 | likely_benign | 0.1939 | benign | -1.141 | Destabilizing | 0.998 | D | 0.587 | neutral | N | 0.401300206 | None | None | I |
| Y/T | 0.3265 | likely_benign | 0.3774 | ambiguous | -0.995 | Destabilizing | 0.999 | D | 0.591 | neutral | None | None | None | None | I |
| Y/V | 0.2731 | likely_benign | 0.3185 | benign | -1.023 | Destabilizing | 0.97 | D | 0.553 | neutral | None | None | None | None | I |
| Y/W | 0.3909 | ambiguous | 0.4369 | ambiguous | -0.397 | Destabilizing | 0.999 | D | 0.565 | 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.