Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14691 | 44296;44297;44298 | chr2:178630887;178630886;178630885 | chr2:179495614;179495613;179495612 |
| N2AB | 13050 | 39373;39374;39375 | chr2:178630887;178630886;178630885 | chr2:179495614;179495613;179495612 |
| N2A | 12123 | 36592;36593;36594 | chr2:178630887;178630886;178630885 | chr2:179495614;179495613;179495612 |
| N2B | 5626 | 17101;17102;17103 | chr2:178630887;178630886;178630885 | chr2:179495614;179495613;179495612 |
| Novex-1 | 5751 | 17476;17477;17478 | chr2:178630887;178630886;178630885 | chr2:179495614;179495613;179495612 |
| Novex-2 | 5818 | 17677;17678;17679 | chr2:178630887;178630886;178630885 | chr2:179495614;179495613;179495612 |
| 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/I | rs1048028645  |
None | 0.999 | D | 0.721 | 0.427 | 0.313210971179 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/I | rs1048028645 |
None | 0.999 | D | 0.721 | 0.427 | 0.313210971179 | gnomAD-4.0.0 | 3.84595E-06 | None | None | None | None | N | None | 3.38352E-05 | 1.69607E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/K | rs1048028645 |
None | 0.999 | D | 0.726 | 0.476 | 0.307966526162 | gnomAD-4.0.0 | 1.59241E-06 | None | None | None | None | N | None | 5.66123E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1573 | likely_benign | 0.1173 | benign | -0.776 | Destabilizing | 0.997 | D | 0.696 | prob.delet. | N | 0.476493096 | None | None | N |
| T/C | 0.7905 | likely_pathogenic | 0.6997 | pathogenic | -0.3 | Destabilizing | 1.0 | D | 0.732 | deleterious | None | None | None | None | N |
| T/D | 0.5282 | ambiguous | 0.4541 | ambiguous | -0.643 | Destabilizing | 0.999 | D | 0.725 | deleterious | None | None | None | None | N |
| T/E | 0.4628 | ambiguous | 0.3698 | ambiguous | -0.635 | Destabilizing | 0.999 | D | 0.726 | deleterious | None | None | None | None | N |
| T/F | 0.5515 | ambiguous | 0.4263 | ambiguous | -0.699 | Destabilizing | 0.999 | D | 0.762 | deleterious | None | None | None | None | N |
| T/G | 0.5627 | ambiguous | 0.4219 | ambiguous | -1.059 | Destabilizing | 0.999 | D | 0.653 | prob.neutral | None | None | None | None | N |
| T/H | 0.5417 | ambiguous | 0.4313 | ambiguous | -1.327 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | N |
| T/I | 0.3659 | ambiguous | 0.3023 | benign | -0.101 | Destabilizing | 0.999 | D | 0.721 | deleterious | D | 0.557646421 | None | None | N |
| T/K | 0.4178 | ambiguous | 0.2816 | benign | -0.959 | Destabilizing | 0.999 | D | 0.726 | deleterious | D | 0.55522625 | None | None | N |
| T/L | 0.2501 | likely_benign | 0.1898 | benign | -0.101 | Destabilizing | 0.998 | D | 0.729 | deleterious | None | None | None | None | N |
| T/M | 0.12 | likely_benign | 0.0964 | benign | 0.277 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| T/N | 0.2166 | likely_benign | 0.1781 | benign | -0.84 | Destabilizing | 0.999 | D | 0.682 | prob.neutral | None | None | None | None | N |
| T/P | 0.239 | likely_benign | 0.1691 | benign | -0.294 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | N | 0.514138802 | None | None | N |
| T/Q | 0.44 | ambiguous | 0.3377 | benign | -0.971 | Destabilizing | 0.999 | D | 0.745 | deleterious | None | None | None | None | N |
| T/R | 0.3685 | ambiguous | 0.2301 | benign | -0.696 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | N | 0.42324922 | None | None | N |
| T/S | 0.1864 | likely_benign | 0.1582 | benign | -1.033 | Destabilizing | 0.997 | D | 0.732 | deleterious | N | 0.42741966 | None | None | N |
| T/V | 0.2898 | likely_benign | 0.2408 | benign | -0.294 | Destabilizing | 0.998 | D | 0.728 | deleterious | None | None | None | None | N |
| T/W | 0.8336 | likely_pathogenic | 0.731 | pathogenic | -0.7 | Destabilizing | 1.0 | D | 0.707 | prob.delet. | None | None | None | None | N |
| T/Y | 0.5853 | likely_pathogenic | 0.455 | ambiguous | -0.502 | Destabilizing | 1.0 | D | 0.767 | deleterious | 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.