Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19399 | 58420;58421;58422 | chr2:178594198;178594197;178594196 | chr2:179458925;179458924;179458923 |
| N2AB | 17758 | 53497;53498;53499 | chr2:178594198;178594197;178594196 | chr2:179458925;179458924;179458923 |
| N2A | 16831 | 50716;50717;50718 | chr2:178594198;178594197;178594196 | chr2:179458925;179458924;179458923 |
| N2B | 10334 | 31225;31226;31227 | chr2:178594198;178594197;178594196 | chr2:179458925;179458924;179458923 |
| Novex-1 | 10459 | 31600;31601;31602 | chr2:178594198;178594197;178594196 | chr2:179458925;179458924;179458923 |
| Novex-2 | 10526 | 31801;31802;31803 | chr2:178594198;178594197;178594196 | chr2:179458925;179458924;179458923 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/P | None | None | 1.0 | D | 0.596 | 0.35 | 0.534046140783 | gnomAD-4.0.0 | 2.05321E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 1.73732E-04 | 1.79916E-06 | 0 | 0 |
| R/Q | rs759893392  |
0.021 | 0.999 | N | 0.531 | 0.296 | 0.370240404367 | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.12575E-04 | None | 3.27E-05 | None | 0 | 6.24E-05 | 0 |
| R/Q | rs759893392 |
0.021 | 0.999 | N | 0.531 | 0.296 | 0.370240404367 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs759893392 |
0.021 | 0.999 | N | 0.531 | 0.296 | 0.370240404367 | gnomAD-4.0.0 | 3.84336E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.47648E-05 | None | 1.56279E-05 | 0 | 4.66253E-05 | 1.09815E-05 | 4.80507E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6837 | likely_pathogenic | 0.6913 | pathogenic | 0.035 | Stabilizing | 0.985 | D | 0.595 | neutral | None | None | None | None | I |
| R/C | 0.3358 | likely_benign | 0.3217 | benign | -0.276 | Destabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | I |
| R/D | 0.891 | likely_pathogenic | 0.8901 | pathogenic | -0.148 | Destabilizing | 0.998 | D | 0.567 | neutral | None | None | None | None | I |
| R/E | 0.6653 | likely_pathogenic | 0.6686 | pathogenic | -0.066 | Destabilizing | 0.985 | D | 0.595 | neutral | None | None | None | None | I |
| R/F | 0.821 | likely_pathogenic | 0.8116 | pathogenic | -0.12 | Destabilizing | 0.999 | D | 0.61 | neutral | None | None | None | None | I |
| R/G | 0.5754 | likely_pathogenic | 0.5732 | pathogenic | -0.174 | Destabilizing | 0.996 | D | 0.571 | neutral | N | 0.486301894 | None | None | I |
| R/H | 0.1969 | likely_benign | 0.1855 | benign | -0.637 | Destabilizing | 0.999 | D | 0.527 | neutral | None | None | None | None | I |
| R/I | 0.5949 | likely_pathogenic | 0.6273 | pathogenic | 0.554 | Stabilizing | 0.999 | D | 0.615 | neutral | None | None | None | None | I |
| R/K | 0.1658 | likely_benign | 0.1743 | benign | -0.117 | Destabilizing | 0.271 | N | 0.383 | neutral | None | None | None | None | I |
| R/L | 0.4404 | ambiguous | 0.4332 | ambiguous | 0.554 | Stabilizing | 0.996 | D | 0.571 | neutral | N | 0.510913403 | None | None | I |
| R/M | 0.5565 | ambiguous | 0.572 | pathogenic | -0.032 | Destabilizing | 1.0 | D | 0.543 | neutral | None | None | None | None | I |
| R/N | 0.8155 | likely_pathogenic | 0.8173 | pathogenic | -0.047 | Destabilizing | 0.998 | D | 0.523 | neutral | None | None | None | None | I |
| R/P | 0.6725 | likely_pathogenic | 0.6594 | pathogenic | 0.402 | Stabilizing | 1.0 | D | 0.596 | neutral | D | 0.526152215 | None | None | I |
| R/Q | 0.1963 | likely_benign | 0.2495 | benign | -0.068 | Destabilizing | 0.999 | D | 0.531 | neutral | N | 0.508353101 | None | None | I |
| R/S | 0.7947 | likely_pathogenic | 0.7952 | pathogenic | -0.335 | Destabilizing | 0.985 | D | 0.604 | neutral | None | None | None | None | I |
| R/T | 0.5719 | likely_pathogenic | 0.5932 | pathogenic | -0.112 | Destabilizing | 0.993 | D | 0.557 | neutral | None | None | None | None | I |
| R/V | 0.6501 | likely_pathogenic | 0.6693 | pathogenic | 0.402 | Stabilizing | 0.998 | D | 0.606 | neutral | None | None | None | None | I |
| R/W | 0.3635 | ambiguous | 0.327 | benign | -0.194 | Destabilizing | 1.0 | D | 0.663 | neutral | None | None | None | None | I |
| R/Y | 0.6861 | likely_pathogenic | 0.6612 | pathogenic | 0.212 | Stabilizing | 0.999 | D | 0.603 | 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.