Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4749 | 14470;14471;14472 | chr2:178738208;178738207;178738206 | chr2:179602935;179602934;179602933 |
| N2AB | 4432 | 13519;13520;13521 | chr2:178738208;178738207;178738206 | chr2:179602935;179602934;179602933 |
| N2A | 3505 | 10738;10739;10740 | chr2:178738208;178738207;178738206 | chr2:179602935;179602934;179602933 |
| N2B | 4386 | 13381;13382;13383 | chr2:178738208;178738207;178738206 | chr2:179602935;179602934;179602933 |
| Novex-1 | 4511 | 13756;13757;13758 | chr2:178738208;178738207;178738206 | chr2:179602935;179602934;179602933 |
| Novex-2 | 4578 | 13957;13958;13959 | chr2:178738208;178738207;178738206 | chr2:179602935;179602934;179602933 |
| 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/G | None | None | 0.249 | N | 0.304 | 0.326 | 0.52551118993 | gnomAD-4.0.0 | 6.84273E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99496E-07 | 0 | 0 |
| R/L | None | None | None | N | 0.157 | 0.327 | 0.488477830397 | gnomAD-4.0.0 | 6.84263E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99488E-07 | 0 | 0 |
| R/Q | rs763823518  |
0.009 | 0.01 | N | 0.194 | 0.268 | 0.195762928549 | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 2.66E-05 | 1.65837E-04 |
| R/Q | rs763823518 |
0.009 | 0.01 | N | 0.194 | 0.268 | 0.195762928549 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 2.88184E-04 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs763823518 |
0.009 | 0.01 | N | 0.194 | 0.268 | 0.195762928549 | gnomAD-4.0.0 | 8.67664E-06 | None | None | None | None | N | None | 0 | 3.33567E-05 | None | 3.37815E-05 | 0 | None | 0 | 0 | 8.47621E-06 | 1.09815E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3754 | ambiguous | 0.5158 | ambiguous | -0.354 | Destabilizing | 0.036 | N | 0.263 | neutral | None | None | None | None | N |
| R/C | 0.1655 | likely_benign | 0.2367 | benign | -0.416 | Destabilizing | 0.901 | D | 0.332 | neutral | None | None | None | None | N |
| R/D | 0.6108 | likely_pathogenic | 0.7566 | pathogenic | -0.047 | Destabilizing | 0.148 | N | 0.406 | neutral | None | None | None | None | N |
| R/E | 0.3489 | ambiguous | 0.4602 | ambiguous | -0.009 | Destabilizing | 0.08 | N | 0.245 | neutral | None | None | None | None | N |
| R/F | 0.4231 | ambiguous | 0.5717 | pathogenic | -0.699 | Destabilizing | 0.174 | N | 0.457 | neutral | None | None | None | None | N |
| R/G | 0.2744 | likely_benign | 0.4211 | ambiguous | -0.51 | Destabilizing | 0.249 | N | 0.304 | neutral | N | 0.479848711 | None | None | N |
| R/H | 0.0807 | likely_benign | 0.0972 | benign | -0.838 | Destabilizing | 0.596 | D | 0.342 | neutral | None | None | None | None | N |
| R/I | 0.2117 | likely_benign | 0.2853 | benign | 0.019 | Stabilizing | 0.001 | N | 0.226 | neutral | None | None | None | None | N |
| R/K | 0.1184 | likely_benign | 0.1417 | benign | -0.281 | Destabilizing | 0.001 | N | 0.105 | neutral | None | None | None | None | N |
| R/L | 0.2178 | likely_benign | 0.3042 | benign | 0.019 | Stabilizing | None | N | 0.157 | neutral | N | 0.478735164 | None | None | N |
| R/M | 0.2957 | likely_benign | 0.4047 | ambiguous | -0.142 | Destabilizing | 0.596 | D | 0.393 | neutral | None | None | None | None | N |
| R/N | 0.4611 | ambiguous | 0.6076 | pathogenic | 0.078 | Stabilizing | 0.148 | N | 0.336 | neutral | None | None | None | None | N |
| R/P | 0.8962 | likely_pathogenic | 0.9512 | pathogenic | -0.087 | Destabilizing | 0.62 | D | 0.481 | neutral | N | 0.480226906 | None | None | N |
| R/Q | 0.0949 | likely_benign | 0.1134 | benign | -0.165 | Destabilizing | 0.01 | N | 0.194 | neutral | N | 0.397192716 | None | None | N |
| R/S | 0.3733 | ambiguous | 0.536 | ambiguous | -0.456 | Destabilizing | 0.007 | N | 0.159 | neutral | None | None | None | None | N |
| R/T | 0.1968 | likely_benign | 0.2832 | benign | -0.298 | Destabilizing | 0.08 | N | 0.309 | neutral | None | None | None | None | N |
| R/V | 0.2961 | likely_benign | 0.3837 | ambiguous | -0.087 | Destabilizing | 0.036 | N | 0.318 | neutral | None | None | None | None | N |
| R/W | 0.1475 | likely_benign | 0.2179 | benign | -0.664 | Destabilizing | 0.749 | D | 0.318 | neutral | None | None | None | None | N |
| R/Y | 0.2896 | likely_benign | 0.4026 | ambiguous | -0.269 | Destabilizing | 0.001 | N | 0.227 | neutral | 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.