Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23058 | 69397;69398;69399 | chr2:178577163;178577162;178577161 | chr2:179441890;179441889;179441888 |
| N2AB | 21417 | 64474;64475;64476 | chr2:178577163;178577162;178577161 | chr2:179441890;179441889;179441888 |
| N2A | 20490 | 61693;61694;61695 | chr2:178577163;178577162;178577161 | chr2:179441890;179441889;179441888 |
| N2B | 13993 | 42202;42203;42204 | chr2:178577163;178577162;178577161 | chr2:179441890;179441889;179441888 |
| Novex-1 | 14118 | 42577;42578;42579 | chr2:178577163;178577162;178577161 | chr2:179441890;179441889;179441888 |
| Novex-2 | 14185 | 42778;42779;42780 | chr2:178577163;178577162;178577161 | chr2:179441890;179441889;179441888 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs752304059  |
-1.034 | 0.919 | N | 0.475 | 0.238 | 0.185906805712 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/A | rs752304059 |
-1.034 | 0.919 | N | 0.475 | 0.238 | 0.185906805712 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| T/A | rs752304059 |
-1.034 | 0.919 | N | 0.475 | 0.238 | 0.185906805712 | gnomAD-4.0.0 | 2.48005E-06 | None | None | None | None | N | None | 2.67201E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47887E-07 | 0 | 1.60226E-05 |
| T/I | None | None | 0.919 | N | 0.575 | 0.397 | 0.345175991111 | gnomAD-4.0.0 | 3.21706E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.22871E-05 | 0 | 0 |
| T/S | rs752304059 |
-1.344 | 0.979 | N | 0.484 | 0.28 | 0.166414681773 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/S | rs752304059 |
-1.344 | 0.979 | N | 0.484 | 0.28 | 0.166414681773 | gnomAD-4.0.0 | 1.30193E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.611E-05 | 0 | 3.20338E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1194 | likely_benign | 0.1216 | benign | -0.973 | Destabilizing | 0.919 | D | 0.475 | neutral | N | 0.521060534 | None | None | N |
| T/C | 0.4799 | ambiguous | 0.4662 | ambiguous | -0.87 | Destabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| T/D | 0.7704 | likely_pathogenic | 0.7797 | pathogenic | -1.173 | Destabilizing | 0.998 | D | 0.701 | prob.neutral | None | None | None | None | N |
| T/E | 0.6207 | likely_pathogenic | 0.6427 | pathogenic | -1.1 | Destabilizing | 0.995 | D | 0.688 | prob.neutral | None | None | None | None | N |
| T/F | 0.2587 | likely_benign | 0.2368 | benign | -0.858 | Destabilizing | 0.991 | D | 0.803 | deleterious | None | None | None | None | N |
| T/G | 0.3986 | ambiguous | 0.4144 | ambiguous | -1.289 | Destabilizing | 0.995 | D | 0.686 | prob.neutral | None | None | None | None | N |
| T/H | 0.434 | ambiguous | 0.4222 | ambiguous | -1.567 | Destabilizing | 1.0 | D | 0.805 | deleterious | None | None | None | None | N |
| T/I | 0.1941 | likely_benign | 0.1964 | benign | -0.198 | Destabilizing | 0.919 | D | 0.575 | neutral | N | 0.484601649 | None | None | N |
| T/K | 0.6061 | likely_pathogenic | 0.6271 | pathogenic | -0.884 | Destabilizing | 0.994 | D | 0.698 | prob.neutral | N | 0.497530313 | None | None | N |
| T/L | 0.1214 | likely_benign | 0.1153 | benign | -0.198 | Destabilizing | 0.938 | D | 0.483 | neutral | None | None | None | None | N |
| T/M | 0.1009 | likely_benign | 0.0991 | benign | -0.02 | Destabilizing | 0.999 | D | 0.748 | deleterious | None | None | None | None | N |
| T/N | 0.2386 | likely_benign | 0.2469 | benign | -1.127 | Destabilizing | 0.998 | D | 0.661 | neutral | None | None | None | None | N |
| T/P | 0.5901 | likely_pathogenic | 0.6453 | pathogenic | -0.424 | Destabilizing | 0.998 | D | 0.725 | prob.delet. | D | 0.538611699 | None | None | N |
| T/Q | 0.4383 | ambiguous | 0.4542 | ambiguous | -1.224 | Destabilizing | 0.998 | D | 0.763 | deleterious | None | None | None | None | N |
| T/R | 0.5126 | ambiguous | 0.5235 | ambiguous | -0.756 | Destabilizing | 0.994 | D | 0.751 | deleterious | N | 0.515595999 | None | None | N |
| T/S | 0.1425 | likely_benign | 0.1374 | benign | -1.326 | Destabilizing | 0.979 | D | 0.484 | neutral | N | 0.4978556 | None | None | N |
| T/V | 0.122 | likely_benign | 0.1198 | benign | -0.424 | Destabilizing | 0.086 | N | 0.439 | neutral | None | None | None | None | N |
| T/W | 0.6891 | likely_pathogenic | 0.6554 | pathogenic | -0.863 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| T/Y | 0.3647 | ambiguous | 0.3524 | ambiguous | -0.574 | Destabilizing | 0.995 | D | 0.806 | deleterious | 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.