Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26603 | 80032;80033;80034 | chr2:178566325;178566324;178566323 | chr2:179431052;179431051;179431050 |
| N2AB | 24962 | 75109;75110;75111 | chr2:178566325;178566324;178566323 | chr2:179431052;179431051;179431050 |
| N2A | 24035 | 72328;72329;72330 | chr2:178566325;178566324;178566323 | chr2:179431052;179431051;179431050 |
| N2B | 17538 | 52837;52838;52839 | chr2:178566325;178566324;178566323 | chr2:179431052;179431051;179431050 |
| Novex-1 | 17663 | 53212;53213;53214 | chr2:178566325;178566324;178566323 | chr2:179431052;179431051;179431050 |
| Novex-2 | 17730 | 53413;53414;53415 | chr2:178566325;178566324;178566323 | chr2:179431052;179431051;179431050 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs376882944  |
-0.474 | 0.006 | D | 0.206 | 0.211 | None | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs376882944 |
-0.474 | 0.006 | D | 0.206 | 0.211 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs376882944 |
-0.474 | 0.006 | D | 0.206 | 0.211 | None | gnomAD-4.0.0 | 3.04521E-06 | None | None | None | None | I | None | 5.24421E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/F | rs914913478 |
-0.539 | 0.627 | N | 0.447 | 0.227 | 0.60543932511 | gnomAD-2.1.1 | 7.14E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.81E-06 | 1.40449E-04 |
| V/F | rs914913478 |
-0.539 | 0.627 | N | 0.447 | 0.227 | 0.60543932511 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/F | rs914913478 |
-0.539 | 0.627 | N | 0.447 | 0.227 | 0.60543932511 | gnomAD-4.0.0 | 2.47912E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.39067E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2099 | likely_benign | 0.1887 | benign | -0.737 | Destabilizing | 0.006 | N | 0.206 | neutral | D | 0.535771775 | None | None | I |
| V/C | 0.6948 | likely_pathogenic | 0.6914 | pathogenic | -0.772 | Destabilizing | 0.981 | D | 0.461 | neutral | None | None | None | None | I |
| V/D | 0.5989 | likely_pathogenic | 0.5287 | ambiguous | -0.407 | Destabilizing | 0.457 | N | 0.467 | neutral | N | 0.487088816 | None | None | I |
| V/E | 0.4548 | ambiguous | 0.4047 | ambiguous | -0.463 | Destabilizing | 0.69 | D | 0.439 | neutral | None | None | None | None | I |
| V/F | 0.2116 | likely_benign | 0.1971 | benign | -0.628 | Destabilizing | 0.627 | D | 0.447 | neutral | N | 0.508017455 | None | None | I |
| V/G | 0.3557 | ambiguous | 0.3357 | benign | -0.948 | Destabilizing | 0.193 | N | 0.458 | neutral | N | 0.514093841 | None | None | I |
| V/H | 0.5947 | likely_pathogenic | 0.574 | pathogenic | -0.373 | Destabilizing | 0.944 | D | 0.467 | neutral | None | None | None | None | I |
| V/I | 0.0672 | likely_benign | 0.0669 | benign | -0.301 | Destabilizing | 0.001 | N | 0.268 | neutral | N | 0.468202776 | None | None | I |
| V/K | 0.5639 | ambiguous | 0.5116 | ambiguous | -0.734 | Destabilizing | 0.69 | D | 0.439 | neutral | None | None | None | None | I |
| V/L | 0.1593 | likely_benign | 0.1477 | benign | -0.301 | Destabilizing | 0.001 | N | 0.188 | neutral | N | 0.502484046 | None | None | I |
| V/M | 0.1332 | likely_benign | 0.1273 | benign | -0.442 | Destabilizing | 0.69 | D | 0.436 | neutral | None | None | None | None | I |
| V/N | 0.2971 | likely_benign | 0.2837 | benign | -0.559 | Destabilizing | 0.005 | N | 0.362 | neutral | None | None | None | None | I |
| V/P | 0.7831 | likely_pathogenic | 0.7612 | pathogenic | -0.41 | Destabilizing | 0.818 | D | 0.472 | neutral | None | None | None | None | I |
| V/Q | 0.3835 | ambiguous | 0.3615 | ambiguous | -0.727 | Destabilizing | 0.69 | D | 0.467 | neutral | None | None | None | None | I |
| V/R | 0.4892 | ambiguous | 0.4497 | ambiguous | -0.224 | Destabilizing | 0.69 | D | 0.483 | neutral | None | None | None | None | I |
| V/S | 0.2212 | likely_benign | 0.2092 | benign | -0.992 | Destabilizing | 0.241 | N | 0.443 | neutral | None | None | None | None | I |
| V/T | 0.1352 | likely_benign | 0.1239 | benign | -0.938 | Destabilizing | 0.388 | N | 0.381 | neutral | None | None | None | None | I |
| V/W | 0.8132 | likely_pathogenic | 0.7981 | pathogenic | -0.747 | Destabilizing | 0.981 | D | 0.624 | neutral | None | None | None | None | I |
| V/Y | 0.5646 | likely_pathogenic | 0.5536 | ambiguous | -0.459 | Destabilizing | 0.818 | D | 0.443 | neutral | None | None | 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.