Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31452 | 94579;94580;94581 | chr2:178547171;178547170;178547169 | chr2:179411898;179411897;179411896 |
| N2AB | 29811 | 89656;89657;89658 | chr2:178547171;178547170;178547169 | chr2:179411898;179411897;179411896 |
| N2A | 28884 | 86875;86876;86877 | chr2:178547171;178547170;178547169 | chr2:179411898;179411897;179411896 |
| N2B | 22387 | 67384;67385;67386 | chr2:178547171;178547170;178547169 | chr2:179411898;179411897;179411896 |
| Novex-1 | 22512 | 67759;67760;67761 | chr2:178547171;178547170;178547169 | chr2:179411898;179411897;179411896 |
| Novex-2 | 22579 | 67960;67961;67962 | chr2:178547171;178547170;178547169 | chr2:179411898;179411897;179411896 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/K | rs1270325139  |
-0.546 | 0.999 | N | 0.551 | 0.372 | 0.370608029945 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.65508E-04 |
| T/K | rs1270325139 |
-0.546 | 0.999 | N | 0.551 | 0.372 | 0.370608029945 | gnomAD-4.0.0 | 1.59117E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88239E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.2045 | likely_benign | 0.2046 | benign | -0.47 | Destabilizing | 0.981 | D | 0.367 | neutral | N | 0.482267285 | None | None | N |
| T/C | 0.7829 | likely_pathogenic | 0.7539 | pathogenic | -0.323 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/D | 0.8672 | likely_pathogenic | 0.8257 | pathogenic | 0.209 | Stabilizing | 0.999 | D | 0.547 | neutral | None | None | None | None | N |
| T/E | 0.8888 | likely_pathogenic | 0.8806 | pathogenic | 0.155 | Stabilizing | 0.999 | D | 0.543 | neutral | None | None | None | None | N |
| T/F | 0.9085 | likely_pathogenic | 0.8954 | pathogenic | -0.798 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| T/G | 0.4034 | ambiguous | 0.3537 | ambiguous | -0.645 | Destabilizing | 0.997 | D | 0.438 | neutral | None | None | None | None | N |
| T/H | 0.7282 | likely_pathogenic | 0.6642 | pathogenic | -0.919 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| T/I | 0.9292 | likely_pathogenic | 0.9205 | pathogenic | -0.121 | Destabilizing | 0.999 | D | 0.581 | neutral | N | 0.463958817 | None | None | N |
| T/K | 0.8502 | likely_pathogenic | 0.8364 | pathogenic | -0.481 | Destabilizing | 0.999 | D | 0.551 | neutral | N | 0.486499669 | None | None | N |
| T/L | 0.5441 | ambiguous | 0.5314 | ambiguous | -0.121 | Destabilizing | 0.998 | D | 0.446 | neutral | None | None | None | None | N |
| T/M | 0.323 | likely_benign | 0.3285 | benign | 0.036 | Stabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| T/N | 0.2798 | likely_benign | 0.2443 | benign | -0.276 | Destabilizing | 0.999 | D | 0.553 | neutral | None | None | None | None | N |
| T/P | 0.9046 | likely_pathogenic | 0.8713 | pathogenic | -0.207 | Destabilizing | 0.999 | D | 0.576 | neutral | N | 0.51359027 | None | None | N |
| T/Q | 0.7088 | likely_pathogenic | 0.671 | pathogenic | -0.478 | Destabilizing | 1.0 | D | 0.604 | neutral | None | None | None | None | N |
| T/R | 0.7869 | likely_pathogenic | 0.7661 | pathogenic | -0.218 | Destabilizing | 0.999 | D | 0.573 | neutral | N | 0.488462539 | None | None | N |
| T/S | 0.1561 | likely_benign | 0.1313 | benign | -0.53 | Destabilizing | 0.905 | D | 0.347 | neutral | N | 0.365034683 | None | None | N |
| T/V | 0.763 | likely_pathogenic | 0.7557 | pathogenic | -0.207 | Destabilizing | 0.998 | D | 0.401 | neutral | None | None | None | None | N |
| T/W | 0.9795 | likely_pathogenic | 0.9711 | pathogenic | -0.773 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/Y | 0.8931 | likely_pathogenic | 0.8628 | pathogenic | -0.517 | Destabilizing | 1.0 | D | 0.671 | 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.