Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29816 | 89671;89672;89673 | chr2:178553559;178553558;178553557 | chr2:179418286;179418285;179418284 |
| N2AB | 28175 | 84748;84749;84750 | chr2:178553559;178553558;178553557 | chr2:179418286;179418285;179418284 |
| N2A | 27248 | 81967;81968;81969 | chr2:178553559;178553558;178553557 | chr2:179418286;179418285;179418284 |
| N2B | 20751 | 62476;62477;62478 | chr2:178553559;178553558;178553557 | chr2:179418286;179418285;179418284 |
| Novex-1 | 20876 | 62851;62852;62853 | chr2:178553559;178553558;178553557 | chr2:179418286;179418285;179418284 |
| Novex-2 | 20943 | 63052;63053;63054 | chr2:178553559;178553558;178553557 | chr2:179418286;179418285;179418284 |
| 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 | rs1202640947  |
-0.244 | 0.961 | N | 0.373 | 0.296 | 0.296679040009 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| A/T | rs1202640947 |
-0.244 | 0.961 | N | 0.373 | 0.296 | 0.296679040009 | gnomAD-4.0.0 | 4.77377E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.57515E-06 | 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 | 0.4198 | ambiguous | 0.475 | ambiguous | -0.77 | Destabilizing | 1.0 | D | 0.439 | neutral | None | None | None | None | I |
| A/D | 0.7873 | likely_pathogenic | 0.8277 | pathogenic | -0.569 | Destabilizing | 0.994 | D | 0.625 | neutral | N | 0.477395946 | None | None | I |
| A/E | 0.5286 | ambiguous | 0.5829 | pathogenic | -0.734 | Destabilizing | 0.97 | D | 0.469 | neutral | None | None | None | None | I |
| A/F | 0.4162 | ambiguous | 0.4715 | ambiguous | -0.928 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | I |
| A/G | 0.2388 | likely_benign | 0.2781 | benign | -0.233 | Destabilizing | 0.98 | D | 0.375 | neutral | N | 0.509726033 | None | None | I |
| A/H | 0.6631 | likely_pathogenic | 0.724 | pathogenic | -0.212 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | I |
| A/I | 0.2443 | likely_benign | 0.2658 | benign | -0.387 | Destabilizing | 0.942 | D | 0.507 | neutral | None | None | None | None | I |
| A/K | 0.6437 | likely_pathogenic | 0.7183 | pathogenic | -0.522 | Destabilizing | 0.155 | N | 0.289 | neutral | None | None | None | None | I |
| A/L | 0.2808 | likely_benign | 0.3292 | benign | -0.387 | Destabilizing | 0.942 | D | 0.455 | neutral | None | None | None | None | I |
| A/M | 0.2887 | likely_benign | 0.3149 | benign | -0.424 | Destabilizing | 0.996 | D | 0.524 | neutral | None | None | None | None | I |
| A/N | 0.5863 | likely_pathogenic | 0.6341 | pathogenic | -0.223 | Destabilizing | 0.996 | D | 0.679 | prob.neutral | None | None | None | None | I |
| A/P | 0.9133 | likely_pathogenic | 0.9285 | pathogenic | -0.303 | Destabilizing | 0.998 | D | 0.521 | neutral | N | 0.490526678 | None | None | I |
| A/Q | 0.4945 | ambiguous | 0.5651 | pathogenic | -0.535 | Destabilizing | 0.991 | D | 0.532 | neutral | None | None | None | None | I |
| A/R | 0.5293 | ambiguous | 0.6102 | pathogenic | -0.023 | Destabilizing | 0.942 | D | 0.485 | neutral | None | None | None | None | I |
| A/S | 0.145 | likely_benign | 0.1545 | benign | -0.393 | Destabilizing | 0.961 | D | 0.409 | neutral | N | 0.511112899 | None | None | I |
| A/T | 0.1698 | likely_benign | 0.1785 | benign | -0.486 | Destabilizing | 0.961 | D | 0.373 | neutral | N | 0.478156414 | None | None | I |
| A/V | 0.1181 | likely_benign | 0.1241 | benign | -0.303 | Destabilizing | 0.248 | N | 0.309 | neutral | N | 0.427206223 | None | None | I |
| A/W | 0.8843 | likely_pathogenic | 0.9144 | pathogenic | -1.027 | Destabilizing | 1.0 | D | 0.755 | deleterious | None | None | None | None | I |
| A/Y | 0.671 | likely_pathogenic | 0.7308 | pathogenic | -0.691 | Destabilizing | 0.999 | D | 0.691 | 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.