Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22562 | 67909;67910;67911 | chr2:178579346;178579345;178579344 | chr2:179444073;179444072;179444071 |
| N2AB | 20921 | 62986;62987;62988 | chr2:178579346;178579345;178579344 | chr2:179444073;179444072;179444071 |
| N2A | 19994 | 60205;60206;60207 | chr2:178579346;178579345;178579344 | chr2:179444073;179444072;179444071 |
| N2B | 13497 | 40714;40715;40716 | chr2:178579346;178579345;178579344 | chr2:179444073;179444072;179444071 |
| Novex-1 | 13622 | 41089;41090;41091 | chr2:178579346;178579345;178579344 | chr2:179444073;179444072;179444071 |
| Novex-2 | 13689 | 41290;41291;41292 | chr2:178579346;178579345;178579344 | chr2:179444073;179444072;179444071 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/D | rs776797528  |
-0.517 | 1.0 | N | 0.675 | 0.567 | 0.829526042196 | gnomAD-2.1.1 | 1.65E-05 | None | None | None | None | I | None | 0 | 0 | None | 2.06186E-04 | 0 | None | 0 | None | 0 | 1.8E-05 | 0 |
| A/D | rs776797528 |
-0.517 | 1.0 | N | 0.675 | 0.567 | 0.829526042196 | gnomAD-4.0.0 | 1.13188E-05 | None | None | None | None | I | None | 0 | 0 | None | 4.83465E-05 | 0 | None | 0 | 0 | 1.73709E-05 | 0 | 0 |
| A/P | rs747962210 |
-0.535 | 1.0 | N | 0.669 | 0.632 | 0.6731056941 | gnomAD-2.1.1 | 4.15E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.65E-05 | None | 0 | None | 0 | 0 | 0 |
| A/P | rs747962210 |
-0.535 | 1.0 | N | 0.669 | 0.632 | 0.6731056941 | gnomAD-4.0.0 | 1.62293E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.7908E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.6345 | likely_pathogenic | 0.6655 | pathogenic | -0.638 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | None | None | None | None | I |
| A/D | 0.9888 | likely_pathogenic | 0.9849 | pathogenic | -1.34 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | N | 0.512994659 | None | None | I |
| A/E | 0.9665 | likely_pathogenic | 0.9546 | pathogenic | -1.169 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | I |
| A/F | 0.8687 | likely_pathogenic | 0.8517 | pathogenic | -0.469 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| A/G | 0.301 | likely_benign | 0.3154 | benign | -1.156 | Destabilizing | 0.999 | D | 0.587 | neutral | N | 0.494129935 | None | None | I |
| A/H | 0.9819 | likely_pathogenic | 0.9775 | pathogenic | -1.602 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | I |
| A/I | 0.5923 | likely_pathogenic | 0.5804 | pathogenic | 0.516 | Stabilizing | 0.994 | D | 0.608 | neutral | None | None | None | None | I |
| A/K | 0.9879 | likely_pathogenic | 0.9824 | pathogenic | -0.866 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| A/L | 0.499 | ambiguous | 0.4865 | ambiguous | 0.516 | Stabilizing | 0.994 | D | 0.471 | neutral | None | None | None | None | I |
| A/M | 0.7158 | likely_pathogenic | 0.6903 | pathogenic | 0.323 | Stabilizing | 1.0 | D | 0.631 | neutral | None | None | None | None | I |
| A/N | 0.9693 | likely_pathogenic | 0.9618 | pathogenic | -1.023 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | I |
| A/P | 0.8777 | likely_pathogenic | 0.8599 | pathogenic | 0.16 | Stabilizing | 1.0 | D | 0.669 | neutral | N | 0.512741169 | None | None | I |
| A/Q | 0.9405 | likely_pathogenic | 0.9231 | pathogenic | -0.839 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | I |
| A/R | 0.9699 | likely_pathogenic | 0.9608 | pathogenic | -1.01 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | I |
| A/S | 0.3736 | ambiguous | 0.3618 | ambiguous | -1.494 | Destabilizing | 0.998 | D | 0.611 | neutral | D | 0.537582716 | None | None | I |
| A/T | 0.4353 | ambiguous | 0.418 | ambiguous | -1.18 | Destabilizing | 0.996 | D | 0.632 | neutral | D | 0.527731082 | None | None | I |
| A/V | 0.2637 | likely_benign | 0.2671 | benign | 0.16 | Stabilizing | 0.767 | D | 0.259 | neutral | N | 0.435121992 | None | None | I |
| A/W | 0.9902 | likely_pathogenic | 0.9881 | pathogenic | -1.189 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | I |
| A/Y | 0.9597 | likely_pathogenic | 0.9497 | pathogenic | -0.556 | Destabilizing | 1.0 | D | 0.696 | prob.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.