Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30066 | 90421;90422;90423 | chr2:178552704;178552703;178552702 | chr2:179417431;179417430;179417429 |
| N2AB | 28425 | 85498;85499;85500 | chr2:178552704;178552703;178552702 | chr2:179417431;179417430;179417429 |
| N2A | 27498 | 82717;82718;82719 | chr2:178552704;178552703;178552702 | chr2:179417431;179417430;179417429 |
| N2B | 21001 | 63226;63227;63228 | chr2:178552704;178552703;178552702 | chr2:179417431;179417430;179417429 |
| Novex-1 | 21126 | 63601;63602;63603 | chr2:178552704;178552703;178552702 | chr2:179417431;179417430;179417429 |
| Novex-2 | 21193 | 63802;63803;63804 | chr2:178552704;178552703;178552702 | chr2:179417431;179417430;179417429 |
| 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 | rs1011515969  |
-1.87 | 0.027 | N | 0.566 | 0.19 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.86E-06 | 0 |
| V/A | rs1011515969 |
-1.87 | 0.027 | N | 0.566 | 0.19 | None | gnomAD-4.0.0 | 3.42086E-06 | None | None | None | None | N | None | 2.98721E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6983E-06 | 0 | 1.6564E-05 |
| V/I | rs1166369536 |
None | None | N | 0.21 | 0.061 | 0.209622950755 | 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 |
| V/I | rs1166369536 |
None | None | N | 0.21 | 0.061 | 0.209622950755 | gnomAD-4.0.0 | 6.57065E-06 | None | None | None | None | N | None | 0 | 0 | None | 2.88184E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1951 | likely_benign | 0.1631 | benign | -2.166 | Highly Destabilizing | 0.027 | N | 0.566 | neutral | N | 0.510552752 | None | None | N |
| V/C | 0.6128 | likely_pathogenic | 0.5444 | ambiguous | -1.47 | Destabilizing | 0.935 | D | 0.607 | neutral | None | None | None | None | N |
| V/D | 0.4859 | ambiguous | 0.3978 | ambiguous | -3.031 | Highly Destabilizing | 0.317 | N | 0.671 | neutral | N | 0.500682475 | None | None | N |
| V/E | 0.3109 | likely_benign | 0.2716 | benign | -2.786 | Highly Destabilizing | 0.38 | N | 0.649 | neutral | None | None | None | None | N |
| V/F | 0.1598 | likely_benign | 0.139 | benign | -1.321 | Destabilizing | 0.188 | N | 0.657 | neutral | N | 0.476768252 | None | None | N |
| V/G | 0.3547 | ambiguous | 0.2771 | benign | -2.698 | Highly Destabilizing | 0.317 | N | 0.684 | prob.neutral | N | 0.471368785 | None | None | N |
| V/H | 0.4389 | ambiguous | 0.3811 | ambiguous | -2.56 | Highly Destabilizing | 0.935 | D | 0.667 | neutral | None | None | None | None | N |
| V/I | 0.0677 | likely_benign | 0.0665 | benign | -0.656 | Destabilizing | None | N | 0.21 | neutral | N | 0.384204808 | None | None | N |
| V/K | 0.361 | ambiguous | 0.3099 | benign | -1.929 | Destabilizing | 0.38 | N | 0.649 | neutral | None | None | None | None | N |
| V/L | 0.1346 | likely_benign | 0.1194 | benign | -0.656 | Destabilizing | None | N | 0.275 | neutral | N | 0.424992638 | None | None | N |
| V/M | 0.1172 | likely_benign | 0.1033 | benign | -0.611 | Destabilizing | 0.235 | N | 0.632 | neutral | None | None | None | None | N |
| V/N | 0.3076 | likely_benign | 0.2536 | benign | -2.346 | Highly Destabilizing | 0.38 | N | 0.656 | neutral | None | None | None | None | N |
| V/P | 0.9541 | likely_pathogenic | 0.925 | pathogenic | -1.137 | Destabilizing | 0.555 | D | 0.625 | neutral | None | None | None | None | N |
| V/Q | 0.2991 | likely_benign | 0.2622 | benign | -2.144 | Highly Destabilizing | 0.555 | D | 0.617 | neutral | None | None | None | None | N |
| V/R | 0.2815 | likely_benign | 0.2423 | benign | -1.761 | Destabilizing | 0.38 | N | 0.675 | neutral | None | None | None | None | N |
| V/S | 0.2473 | likely_benign | 0.2014 | benign | -2.872 | Highly Destabilizing | 0.081 | N | 0.642 | neutral | None | None | None | None | N |
| V/T | 0.1618 | likely_benign | 0.1396 | benign | -2.497 | Highly Destabilizing | 0.001 | N | 0.446 | neutral | None | None | None | None | N |
| V/W | 0.7147 | likely_pathogenic | 0.6457 | pathogenic | -1.953 | Destabilizing | 0.935 | D | 0.687 | prob.neutral | None | None | None | None | N |
| V/Y | 0.4555 | ambiguous | 0.3985 | ambiguous | -1.548 | Destabilizing | 0.555 | D | 0.639 | 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.