Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14647 | 44164;44165;44166 | chr2:178631109;178631108;178631107 | chr2:179495836;179495835;179495834 |
| N2AB | 13006 | 39241;39242;39243 | chr2:178631109;178631108;178631107 | chr2:179495836;179495835;179495834 |
| N2A | 12079 | 36460;36461;36462 | chr2:178631109;178631108;178631107 | chr2:179495836;179495835;179495834 |
| N2B | 5582 | 16969;16970;16971 | chr2:178631109;178631108;178631107 | chr2:179495836;179495835;179495834 |
| Novex-1 | 5707 | 17344;17345;17346 | chr2:178631109;178631108;178631107 | chr2:179495836;179495835;179495834 |
| Novex-2 | 5774 | 17545;17546;17547 | chr2:178631109;178631108;178631107 | chr2:179495836;179495835;179495834 |
| 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/T | None | None | 0.009 | N | 0.375 | 0.115 | 0.249502417897 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 6.17284E-04 | 0 | 0 | 0 |
| A/V | rs1647945461  |
None | 0.009 | N | 0.377 | 0.227 | 0.249502417897 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/V | rs1647945461 |
None | 0.009 | N | 0.377 | 0.227 | 0.249502417897 | gnomAD-4.0.0 | 6.57765E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47076E-05 | 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 | 0.7457 | likely_pathogenic | 0.7512 | pathogenic | -1.495 | Destabilizing | 0.968 | D | 0.587 | neutral | None | None | None | None | N |
| A/D | 0.9182 | likely_pathogenic | 0.9524 | pathogenic | -2.359 | Highly Destabilizing | 0.497 | N | 0.695 | prob.neutral | D | 0.618878644 | None | None | N |
| A/E | 0.8844 | likely_pathogenic | 0.9328 | pathogenic | -2.32 | Highly Destabilizing | 0.567 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/F | 0.8239 | likely_pathogenic | 0.8488 | pathogenic | -1.147 | Destabilizing | 0.726 | D | 0.702 | prob.neutral | None | None | None | None | N |
| A/G | 0.3033 | likely_benign | 0.3159 | benign | -1.551 | Destabilizing | 0.22 | N | 0.522 | neutral | D | 0.674846086 | None | None | N |
| A/H | 0.9419 | likely_pathogenic | 0.9638 | pathogenic | -1.671 | Destabilizing | 0.968 | D | 0.679 | prob.neutral | None | None | None | None | N |
| A/I | 0.4774 | ambiguous | 0.505 | ambiguous | -0.451 | Destabilizing | 0.157 | N | 0.635 | neutral | None | None | None | None | N |
| A/K | 0.9592 | likely_pathogenic | 0.9793 | pathogenic | -1.503 | Destabilizing | 0.567 | D | 0.675 | neutral | None | None | None | None | N |
| A/L | 0.417 | ambiguous | 0.4855 | ambiguous | -0.451 | Destabilizing | 0.157 | N | 0.561 | neutral | None | None | None | None | N |
| A/M | 0.5942 | likely_pathogenic | 0.6422 | pathogenic | -0.514 | Destabilizing | 0.909 | D | 0.657 | neutral | None | None | None | None | N |
| A/N | 0.8011 | likely_pathogenic | 0.8583 | pathogenic | -1.491 | Destabilizing | 0.567 | D | 0.705 | prob.neutral | None | None | None | None | N |
| A/P | 0.1573 | likely_benign | 0.3325 | benign | -0.67 | Destabilizing | 0.002 | N | 0.399 | neutral | D | 0.600362625 | None | None | N |
| A/Q | 0.8855 | likely_pathogenic | 0.93 | pathogenic | -1.6 | Destabilizing | 0.726 | D | 0.672 | neutral | None | None | None | None | N |
| A/R | 0.9225 | likely_pathogenic | 0.9536 | pathogenic | -1.2 | Destabilizing | 0.726 | D | 0.695 | prob.neutral | None | None | None | None | N |
| A/S | 0.2051 | likely_benign | 0.2187 | benign | -1.833 | Destabilizing | 0.124 | N | 0.513 | neutral | D | 0.571603168 | None | None | N |
| A/T | 0.1834 | likely_benign | 0.2084 | benign | -1.701 | Destabilizing | 0.009 | N | 0.375 | neutral | N | 0.519670526 | None | None | N |
| A/V | 0.2011 | likely_benign | 0.2106 | benign | -0.67 | Destabilizing | 0.009 | N | 0.377 | neutral | N | 0.45474077 | None | None | N |
| A/W | 0.9781 | likely_pathogenic | 0.9855 | pathogenic | -1.605 | Destabilizing | 0.968 | D | 0.701 | prob.neutral | None | None | None | None | N |
| A/Y | 0.924 | likely_pathogenic | 0.9427 | pathogenic | -1.194 | Destabilizing | 0.89 | D | 0.703 | prob.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.