Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2222 | 6889;6890;6891 | chr2:178775047;178775046;178775045 | chr2:179639774;179639773;179639772 |
| N2AB | 2222 | 6889;6890;6891 | chr2:178775047;178775046;178775045 | chr2:179639774;179639773;179639772 |
| N2A | 2222 | 6889;6890;6891 | chr2:178775047;178775046;178775045 | chr2:179639774;179639773;179639772 |
| N2B | 2176 | 6751;6752;6753 | chr2:178775047;178775046;178775045 | chr2:179639774;179639773;179639772 |
| Novex-1 | 2176 | 6751;6752;6753 | chr2:178775047;178775046;178775045 | chr2:179639774;179639773;179639772 |
| Novex-2 | 2176 | 6751;6752;6753 | chr2:178775047;178775046;178775045 | chr2:179639774;179639773;179639772 |
| Novex-3 | 2222 | 6889;6890;6891 | chr2:178775047;178775046;178775045 | chr2:179639774;179639773;179639772 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/K | None | None | 0.324 | D | 0.517 | 0.495 | 0.656780015411 | gnomAD-4.0.0 | 6.84119E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15934E-05 | 0 |
| M/T | rs757071471  |
-1.272 | 0.001 | N | 0.259 | 0.31 | 0.726310685241 | gnomAD-2.1.1 | 1.59E-05 | None | None | None | None | N | None | 0 | 1.15727E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs757071471 |
-1.272 | 0.001 | N | 0.259 | 0.31 | 0.726310685241 | gnomAD-4.0.0 | 2.73648E-06 | None | None | None | None | N | None | 0 | 8.94454E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/V | rs1212976670 |
-0.83 | 0.09 | N | 0.388 | 0.298 | 0.4722639086 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 2.89E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/V | rs1212976670 |
-0.83 | 0.09 | N | 0.388 | 0.298 | 0.4722639086 | gnomAD-4.0.0 | 1.59079E-06 | None | None | None | None | N | None | 0 | 2.28645E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.4033 | ambiguous | 0.3876 | ambiguous | -2.466 | Highly Destabilizing | 0.116 | N | 0.437 | neutral | None | None | None | None | N |
| M/C | 0.7013 | likely_pathogenic | 0.6976 | pathogenic | -1.532 | Destabilizing | 0.944 | D | 0.535 | neutral | None | None | None | None | N |
| M/D | 0.891 | likely_pathogenic | 0.898 | pathogenic | -1.192 | Destabilizing | 0.69 | D | 0.631 | neutral | None | None | None | None | N |
| M/E | 0.5207 | ambiguous | 0.5296 | ambiguous | -1.086 | Destabilizing | 0.388 | N | 0.565 | neutral | None | None | None | None | N |
| M/F | 0.3401 | ambiguous | 0.3414 | ambiguous | -1.125 | Destabilizing | 0.818 | D | 0.515 | neutral | None | None | None | None | N |
| M/G | 0.6195 | likely_pathogenic | 0.6245 | pathogenic | -2.857 | Highly Destabilizing | 0.388 | N | 0.596 | neutral | None | None | None | None | N |
| M/H | 0.5377 | ambiguous | 0.5303 | ambiguous | -1.924 | Destabilizing | 0.981 | D | 0.574 | neutral | None | None | None | None | N |
| M/I | 0.3215 | likely_benign | 0.3129 | benign | -1.389 | Destabilizing | 0.193 | N | 0.51 | neutral | N | 0.467054117 | None | None | N |
| M/K | 0.1683 | likely_benign | 0.1558 | benign | -1.138 | Destabilizing | 0.324 | N | 0.517 | neutral | D | 0.66809434 | None | None | N |
| M/L | 0.1651 | likely_benign | 0.1515 | benign | -1.389 | Destabilizing | 0.041 | N | 0.279 | neutral | N | 0.505416429 | None | None | N |
| M/N | 0.5229 | ambiguous | 0.5247 | ambiguous | -1.096 | Destabilizing | 0.69 | D | 0.591 | neutral | None | None | None | None | N |
| M/P | 0.7787 | likely_pathogenic | 0.797 | pathogenic | -1.726 | Destabilizing | 0.818 | D | 0.596 | neutral | None | None | None | None | N |
| M/Q | 0.2152 | likely_benign | 0.2117 | benign | -1.061 | Destabilizing | 0.818 | D | 0.517 | neutral | None | None | None | None | N |
| M/R | 0.1971 | likely_benign | 0.1806 | benign | -0.759 | Destabilizing | 0.627 | D | 0.546 | neutral | D | 0.589537444 | None | None | N |
| M/S | 0.3707 | ambiguous | 0.371 | ambiguous | -1.765 | Destabilizing | 0.241 | N | 0.513 | neutral | None | None | None | None | N |
| M/T | 0.1463 | likely_benign | 0.1386 | benign | -1.543 | Destabilizing | 0.001 | N | 0.259 | neutral | N | 0.501400244 | None | None | N |
| M/V | 0.1322 | likely_benign | 0.1208 | benign | -1.726 | Destabilizing | 0.09 | N | 0.388 | neutral | N | 0.498196464 | None | None | N |
| M/W | 0.6686 | likely_pathogenic | 0.6672 | pathogenic | -1.111 | Destabilizing | 0.981 | D | 0.546 | neutral | None | None | None | None | N |
| M/Y | 0.6289 | likely_pathogenic | 0.6221 | pathogenic | -1.219 | Destabilizing | 0.818 | D | 0.558 | 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.