Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23978 | 72157;72158;72159 | chr2:178574200;178574199;178574198 | chr2:179438927;179438926;179438925 |
| N2AB | 22337 | 67234;67235;67236 | chr2:178574200;178574199;178574198 | chr2:179438927;179438926;179438925 |
| N2A | 21410 | 64453;64454;64455 | chr2:178574200;178574199;178574198 | chr2:179438927;179438926;179438925 |
| N2B | 14913 | 44962;44963;44964 | chr2:178574200;178574199;178574198 | chr2:179438927;179438926;179438925 |
| Novex-1 | 15038 | 45337;45338;45339 | chr2:178574200;178574199;178574198 | chr2:179438927;179438926;179438925 |
| Novex-2 | 15105 | 45538;45539;45540 | chr2:178574200;178574199;178574198 | chr2:179438927;179438926;179438925 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | rs1346537219  |
-0.64 | 1.0 | N | 0.708 | 0.495 | 0.252162846088 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| N/H | rs1346537219 |
-0.64 | 1.0 | N | 0.708 | 0.495 | 0.252162846088 | gnomAD-4.0.0 | 1.59203E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85956E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3002 | likely_benign | 0.3213 | benign | -0.392 | Destabilizing | 1.0 | D | 0.747 | deleterious | None | None | None | None | I |
| N/C | 0.4671 | ambiguous | 0.4775 | ambiguous | 0.297 | Stabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | I |
| N/D | 0.321 | likely_benign | 0.3027 | benign | 0.245 | Stabilizing | 0.999 | D | 0.613 | neutral | N | 0.511496901 | None | None | I |
| N/E | 0.7324 | likely_pathogenic | 0.7235 | pathogenic | 0.194 | Stabilizing | 0.999 | D | 0.683 | prob.neutral | None | None | None | None | I |
| N/F | 0.7673 | likely_pathogenic | 0.7911 | pathogenic | -0.875 | Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | I |
| N/G | 0.3517 | ambiguous | 0.3608 | ambiguous | -0.523 | Destabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | I |
| N/H | 0.1873 | likely_benign | 0.1925 | benign | -0.597 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | N | 0.471079296 | None | None | I |
| N/I | 0.346 | ambiguous | 0.37 | ambiguous | -0.138 | Destabilizing | 1.0 | D | 0.872 | deleterious | N | 0.512190335 | None | None | I |
| N/K | 0.6584 | likely_pathogenic | 0.662 | pathogenic | 0.259 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | N | 0.498258245 | None | None | I |
| N/L | 0.3653 | ambiguous | 0.3909 | ambiguous | -0.138 | Destabilizing | 1.0 | D | 0.841 | deleterious | None | None | None | None | I |
| N/M | 0.5046 | ambiguous | 0.5379 | ambiguous | 0.264 | Stabilizing | 1.0 | D | 0.811 | deleterious | None | None | None | None | I |
| N/P | 0.5095 | ambiguous | 0.4912 | ambiguous | -0.198 | Destabilizing | 1.0 | D | 0.861 | deleterious | None | None | None | None | I |
| N/Q | 0.5709 | likely_pathogenic | 0.5801 | pathogenic | -0.251 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | I |
| N/R | 0.6918 | likely_pathogenic | 0.7035 | pathogenic | 0.311 | Stabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | I |
| N/S | 0.0906 | likely_benign | 0.0945 | benign | -0.019 | Destabilizing | 0.999 | D | 0.603 | neutral | N | 0.515035852 | None | None | I |
| N/T | 0.1785 | likely_benign | 0.1809 | benign | 0.071 | Stabilizing | 0.999 | D | 0.673 | neutral | N | 0.494335293 | None | None | I |
| N/V | 0.2961 | likely_benign | 0.3191 | benign | -0.198 | Destabilizing | 1.0 | D | 0.858 | deleterious | None | None | None | None | I |
| N/W | 0.932 | likely_pathogenic | 0.9354 | pathogenic | -0.853 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | I |
| N/Y | 0.3518 | ambiguous | 0.3606 | ambiguous | -0.574 | Destabilizing | 1.0 | D | 0.843 | deleterious | N | 0.498235679 | 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.