Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14780 | 44563;44564;44565 | chr2:178629387;178629386;178629385 | chr2:179494114;179494113;179494112 |
| N2AB | 13139 | 39640;39641;39642 | chr2:178629387;178629386;178629385 | chr2:179494114;179494113;179494112 |
| N2A | 12212 | 36859;36860;36861 | chr2:178629387;178629386;178629385 | chr2:179494114;179494113;179494112 |
| N2B | 5715 | 17368;17369;17370 | chr2:178629387;178629386;178629385 | chr2:179494114;179494113;179494112 |
| Novex-1 | 5840 | 17743;17744;17745 | chr2:178629387;178629386;178629385 | chr2:179494114;179494113;179494112 |
| Novex-2 | 5907 | 17944;17945;17946 | chr2:178629387;178629386;178629385 | chr2:179494114;179494113;179494112 |
| 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/A | rs1279825946  |
-0.656 | 0.76 | N | 0.39 | 0.125 | 0.115124310173 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| T/A | rs1279825946 |
-0.656 | 0.76 | N | 0.39 | 0.125 | 0.115124310173 | gnomAD-4.0.0 | 3.18617E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86156E-06 | 1.43328E-05 | 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 | 0.1404 | likely_benign | 0.1426 | benign | -0.728 | Destabilizing | 0.76 | D | 0.39 | neutral | N | 0.448442032 | None | None | N |
| T/C | 0.7317 | likely_pathogenic | 0.7253 | pathogenic | -0.39 | Destabilizing | 0.999 | D | 0.697 | prob.neutral | None | None | None | None | N |
| T/D | 0.5153 | ambiguous | 0.4894 | ambiguous | -0.192 | Destabilizing | 0.986 | D | 0.651 | neutral | None | None | None | None | N |
| T/E | 0.4628 | ambiguous | 0.4746 | ambiguous | -0.224 | Destabilizing | 0.986 | D | 0.647 | neutral | None | None | None | None | N |
| T/F | 0.5182 | ambiguous | 0.5589 | ambiguous | -0.921 | Destabilizing | 0.998 | D | 0.781 | deleterious | None | None | None | None | N |
| T/G | 0.4043 | ambiguous | 0.3671 | ambiguous | -0.95 | Destabilizing | 0.91 | D | 0.551 | neutral | None | None | None | None | N |
| T/H | 0.5206 | ambiguous | 0.5009 | ambiguous | -1.251 | Destabilizing | 0.999 | D | 0.751 | deleterious | None | None | None | None | N |
| T/I | 0.4814 | ambiguous | 0.5757 | pathogenic | -0.241 | Destabilizing | 0.991 | D | 0.715 | prob.delet. | D | 0.594999367 | None | None | N |
| T/K | 0.4051 | ambiguous | 0.456 | ambiguous | -0.702 | Destabilizing | 0.982 | D | 0.653 | neutral | N | 0.451978099 | None | None | N |
| T/L | 0.2625 | likely_benign | 0.308 | benign | -0.241 | Destabilizing | 0.953 | D | 0.554 | neutral | None | None | None | None | N |
| T/M | 0.1401 | likely_benign | 0.1504 | benign | 0.117 | Stabilizing | 0.999 | D | 0.696 | prob.neutral | None | None | None | None | N |
| T/N | 0.1946 | likely_benign | 0.1893 | benign | -0.544 | Destabilizing | 0.986 | D | 0.569 | neutral | None | None | None | None | N |
| T/P | 0.2858 | likely_benign | 0.2907 | benign | -0.372 | Destabilizing | 0.991 | D | 0.719 | prob.delet. | N | 0.445079417 | None | None | N |
| T/Q | 0.4232 | ambiguous | 0.4289 | ambiguous | -0.776 | Destabilizing | 0.993 | D | 0.723 | prob.delet. | None | None | None | None | N |
| T/R | 0.3679 | ambiguous | 0.4095 | ambiguous | -0.402 | Destabilizing | 0.982 | D | 0.732 | prob.delet. | N | 0.456097746 | None | None | N |
| T/S | 0.1438 | likely_benign | 0.1252 | benign | -0.806 | Destabilizing | 0.17 | N | 0.203 | neutral | N | 0.431004082 | None | None | N |
| T/V | 0.3437 | ambiguous | 0.4145 | ambiguous | -0.372 | Destabilizing | 0.953 | D | 0.481 | neutral | None | None | None | None | N |
| T/W | 0.8088 | likely_pathogenic | 0.7956 | pathogenic | -0.848 | Destabilizing | 0.999 | D | 0.755 | deleterious | None | None | None | None | N |
| T/Y | 0.5136 | ambiguous | 0.5159 | ambiguous | -0.622 | Destabilizing | 0.998 | D | 0.781 | 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.