Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34144 | 102655;102656;102657 | chr2:178534185;178534184;178534183 | chr2:179398912;179398911;179398910 |
| N2AB | 32503 | 97732;97733;97734 | chr2:178534185;178534184;178534183 | chr2:179398912;179398911;179398910 |
| N2A | 31576 | 94951;94952;94953 | chr2:178534185;178534184;178534183 | chr2:179398912;179398911;179398910 |
| N2B | 25079 | 75460;75461;75462 | chr2:178534185;178534184;178534183 | chr2:179398912;179398911;179398910 |
| Novex-1 | 25204 | 75835;75836;75837 | chr2:178534185;178534184;178534183 | chr2:179398912;179398911;179398910 |
| Novex-2 | 25271 | 76036;76037;76038 | chr2:178534185;178534184;178534183 | chr2:179398912;179398911;179398910 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/Q | None | None | 0.997 | N | 0.476 | 0.239 | 0.434497104326 | gnomAD-4.0.0 | 1.36831E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.51902E-05 | None | 0 | 0 | 0 | 0 | 1.6564E-05 |
| H/R | rs1553495003  |
None | 0.997 | N | 0.469 | 0.488 | 0.416707687347 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.66327E-05 |
| H/Y | rs560027565 |
1.224 | 0.997 | N | 0.471 | 0.445 | 0.433157607263 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| H/Y | rs560027565 |
1.224 | 0.997 | N | 0.471 | 0.445 | 0.433157607263 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.92753E-04 | None | 0 | 0 | 0 | 0 | 0 |
| H/Y | rs560027565 |
1.224 | 0.997 | N | 0.471 | 0.445 | 0.433157607263 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 1E-03 | 0 | None | None | None | 0 | None |
| H/Y | rs560027565 |
1.224 | 0.997 | N | 0.471 | 0.445 | 0.433157607263 | gnomAD-4.0.0 | 6.56676E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.93199E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.7702 | likely_pathogenic | 0.8361 | pathogenic | -0.198 | Destabilizing | 0.993 | D | 0.481 | neutral | None | None | None | None | I |
| H/C | 0.6723 | likely_pathogenic | 0.7217 | pathogenic | 0.472 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | I |
| H/D | 0.5668 | likely_pathogenic | 0.6844 | pathogenic | -0.349 | Destabilizing | 0.961 | D | 0.497 | neutral | N | 0.395603598 | None | None | I |
| H/E | 0.7391 | likely_pathogenic | 0.797 | pathogenic | -0.267 | Destabilizing | 0.985 | D | 0.436 | neutral | None | None | None | None | I |
| H/F | 0.7615 | likely_pathogenic | 0.7732 | pathogenic | 0.958 | Stabilizing | 0.999 | D | 0.552 | neutral | None | None | None | None | I |
| H/G | 0.7279 | likely_pathogenic | 0.8144 | pathogenic | -0.544 | Destabilizing | 0.985 | D | 0.473 | neutral | None | None | None | None | I |
| H/I | 0.9013 | likely_pathogenic | 0.9201 | pathogenic | 0.736 | Stabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | I |
| H/K | 0.755 | likely_pathogenic | 0.8016 | pathogenic | 0.033 | Stabilizing | 0.985 | D | 0.501 | neutral | None | None | None | None | I |
| H/L | 0.5116 | ambiguous | 0.5332 | ambiguous | 0.736 | Stabilizing | 0.997 | D | 0.549 | neutral | N | 0.484900238 | None | None | I |
| H/M | 0.8746 | likely_pathogenic | 0.8946 | pathogenic | 0.443 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | I |
| H/N | 0.281 | likely_benign | 0.3899 | ambiguous | -0.168 | Destabilizing | 0.4 | N | 0.199 | neutral | N | 0.416096301 | None | None | I |
| H/P | 0.5213 | ambiguous | 0.5112 | ambiguous | 0.447 | Stabilizing | 0.999 | D | 0.629 | neutral | N | 0.46483161 | None | None | I |
| H/Q | 0.6307 | likely_pathogenic | 0.7115 | pathogenic | 0.016 | Stabilizing | 0.997 | D | 0.476 | neutral | N | 0.483860088 | None | None | I |
| H/R | 0.56 | ambiguous | 0.6222 | pathogenic | -0.552 | Destabilizing | 0.997 | D | 0.469 | neutral | N | 0.454057256 | None | None | I |
| H/S | 0.5926 | likely_pathogenic | 0.7209 | pathogenic | -0.095 | Destabilizing | 0.985 | D | 0.473 | neutral | None | None | None | None | I |
| H/T | 0.8075 | likely_pathogenic | 0.8743 | pathogenic | 0.099 | Stabilizing | 0.996 | D | 0.485 | neutral | None | None | None | None | I |
| H/V | 0.8493 | likely_pathogenic | 0.8743 | pathogenic | 0.447 | Stabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | I |
| H/W | 0.7963 | likely_pathogenic | 0.813 | pathogenic | 1.173 | Stabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | I |
| H/Y | 0.374 | ambiguous | 0.4072 | ambiguous | 1.262 | Stabilizing | 0.997 | D | 0.471 | neutral | N | 0.485246955 | 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.