Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26981 | 81166;81167;81168 | chr2:178565191;178565190;178565189 | chr2:179429918;179429917;179429916 |
| N2AB | 25340 | 76243;76244;76245 | chr2:178565191;178565190;178565189 | chr2:179429918;179429917;179429916 |
| N2A | 24413 | 73462;73463;73464 | chr2:178565191;178565190;178565189 | chr2:179429918;179429917;179429916 |
| N2B | 17916 | 53971;53972;53973 | chr2:178565191;178565190;178565189 | chr2:179429918;179429917;179429916 |
| Novex-1 | 18041 | 54346;54347;54348 | chr2:178565191;178565190;178565189 | chr2:179429918;179429917;179429916 |
| Novex-2 | 18108 | 54547;54548;54549 | chr2:178565191;178565190;178565189 | chr2:179429918;179429917;179429916 |
| 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/L | None | None | 0.251 | D | 0.559 | 0.127 | 0.400613892164 | gnomAD-4.0.0 | 1.36867E-06 | None | None | None | None | N | None | 0 | 0 | None | 3.82936E-05 | 0 | None | 0 | 0 | 8.99567E-07 | 0 | 0 |
| R/Q | rs768308408  |
-0.477 | 0.271 | N | 0.517 | 0.088 | 0.119812018005 | gnomAD-2.1.1 | 3.58E-05 | None | None | None | None | N | None | 0 | 5.66E-05 | None | 0 | 5.14E-05 | None | 6.54E-05 | None | 0 | 2.35E-05 | 2.81215E-04 |
| R/Q | rs768308408 |
-0.477 | 0.271 | N | 0.517 | 0.088 | 0.119812018005 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | N | None | 0 | 3.27611E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/Q | rs768308408 |
-0.477 | 0.271 | N | 0.517 | 0.088 | 0.119812018005 | gnomAD-4.0.0 | 9.48326E-05 | None | None | None | None | N | None | 1.33543E-05 | 1.16717E-04 | None | 0 | 0 | None | 0 | 0 | 1.00877E-04 | 2.08709E-04 | 1.12108E-04 |
| R/W | rs779878975 |
-0.477 | 0.984 | N | 0.657 | 0.267 | 0.313818047136 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.57E-05 | 1.66058E-04 |
| R/W | rs779878975 |
-0.477 | 0.984 | N | 0.657 | 0.267 | 0.313818047136 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 1.93199E-04 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/W | rs779878975 |
-0.477 | 0.984 | N | 0.657 | 0.267 | 0.313818047136 | gnomAD-4.0.0 | 3.28501E-05 | None | None | None | None | N | None | 2.67087E-05 | 1.16733E-04 | None | 0 | 2.23095E-05 | None | 0 | 0 | 3.4756E-05 | 0 | 3.20297E-05 |
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 | 0.2931 | likely_benign | 0.2618 | benign | -0.875 | Destabilizing | 0.035 | N | 0.521 | neutral | None | None | None | None | N |
| R/C | 0.1139 | likely_benign | 0.1142 | benign | -0.85 | Destabilizing | 0.935 | D | 0.597 | neutral | None | None | None | None | N |
| R/D | 0.5369 | ambiguous | 0.5081 | ambiguous | -0.079 | Destabilizing | 0.081 | N | 0.557 | neutral | None | None | None | None | N |
| R/E | 0.296 | likely_benign | 0.2674 | benign | 0.054 | Stabilizing | 0.035 | N | 0.517 | neutral | None | None | None | None | N |
| R/F | 0.429 | ambiguous | 0.3796 | ambiguous | -0.687 | Destabilizing | 0.791 | D | 0.579 | neutral | None | None | None | None | N |
| R/G | 0.251 | likely_benign | 0.236 | benign | -1.196 | Destabilizing | 0.144 | N | 0.559 | neutral | N | 0.474953637 | None | None | N |
| R/H | 0.077 | likely_benign | 0.0759 | benign | -1.473 | Destabilizing | 0.555 | D | 0.533 | neutral | None | None | None | None | N |
| R/I | 0.153 | likely_benign | 0.1352 | benign | -0.008 | Destabilizing | 0.555 | D | 0.595 | neutral | None | None | None | None | N |
| R/K | 0.0769 | likely_benign | 0.0672 | benign | -0.895 | Destabilizing | None | N | 0.121 | neutral | None | None | None | None | N |
| R/L | 0.1743 | likely_benign | 0.1523 | benign | -0.008 | Destabilizing | 0.251 | N | 0.559 | neutral | D | 0.522503329 | None | None | N |
| R/M | 0.2015 | likely_benign | 0.179 | benign | -0.349 | Destabilizing | 0.791 | D | 0.557 | neutral | None | None | None | None | N |
| R/N | 0.3594 | ambiguous | 0.3196 | benign | -0.383 | Destabilizing | 0.001 | N | 0.193 | neutral | None | None | None | None | N |
| R/P | 0.8907 | likely_pathogenic | 0.8765 | pathogenic | -0.276 | Destabilizing | 0.705 | D | 0.577 | neutral | N | 0.502212151 | None | None | N |
| R/Q | 0.0881 | likely_benign | 0.0846 | benign | -0.525 | Destabilizing | 0.271 | N | 0.517 | neutral | N | 0.463222952 | None | None | N |
| R/S | 0.3188 | likely_benign | 0.2931 | benign | -1.173 | Destabilizing | 0.035 | N | 0.545 | neutral | None | None | None | None | N |
| R/T | 0.1529 | likely_benign | 0.1387 | benign | -0.85 | Destabilizing | 0.149 | N | 0.555 | neutral | None | None | None | None | N |
| R/V | 0.204 | likely_benign | 0.1729 | benign | -0.276 | Destabilizing | 0.149 | N | 0.597 | neutral | None | None | None | None | N |
| R/W | 0.2086 | likely_benign | 0.2001 | benign | -0.321 | Destabilizing | 0.984 | D | 0.657 | neutral | N | 0.502465641 | None | None | N |
| R/Y | 0.3089 | likely_benign | 0.2774 | benign | -0.034 | Destabilizing | 0.791 | D | 0.586 | 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.