Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22329 | 67210;67211;67212 | chr2:178580394;178580393;178580392 | chr2:179445121;179445120;179445119 |
| N2AB | 20688 | 62287;62288;62289 | chr2:178580394;178580393;178580392 | chr2:179445121;179445120;179445119 |
| N2A | 19761 | 59506;59507;59508 | chr2:178580394;178580393;178580392 | chr2:179445121;179445120;179445119 |
| N2B | 13264 | 40015;40016;40017 | chr2:178580394;178580393;178580392 | chr2:179445121;179445120;179445119 |
| Novex-1 | 13389 | 40390;40391;40392 | chr2:178580394;178580393;178580392 | chr2:179445121;179445120;179445119 |
| Novex-2 | 13456 | 40591;40592;40593 | chr2:178580394;178580393;178580392 | chr2:179445121;179445120;179445119 |
| 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/E | rs2047425169  |
None | 0.988 | D | 0.742 | 0.519 | 0.681754529401 | gnomAD-4.0.0 | 6.84446E-07 | None | None | None | None | I | None | 2.99079E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/S | rs886055253 |
-1.047 | 0.414 | N | 0.367 | 0.104 | 0.207176502487 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| A/S | rs886055253 |
-1.047 | 0.414 | N | 0.367 | 0.104 | 0.207176502487 | gnomAD-4.0.0 | 6.84437E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99708E-07 | 0 | 0 |
| A/T | rs886055253 |
-0.908 | 0.919 | D | 0.576 | 0.279 | 0.373173300195 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| A/T | rs886055253 |
-0.908 | 0.919 | D | 0.576 | 0.279 | 0.373173300195 | gnomAD-4.0.0 | 5.4755E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.19766E-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 | 0.656 | likely_pathogenic | 0.6864 | pathogenic | -0.834 | Destabilizing | 1.0 | D | 0.767 | deleterious | None | None | None | None | I |
| A/D | 0.9189 | likely_pathogenic | 0.9387 | pathogenic | -0.718 | Destabilizing | 0.991 | D | 0.821 | deleterious | None | None | None | None | I |
| A/E | 0.8309 | likely_pathogenic | 0.8673 | pathogenic | -0.805 | Destabilizing | 0.988 | D | 0.742 | deleterious | D | 0.523359839 | None | None | I |
| A/F | 0.8303 | likely_pathogenic | 0.8317 | pathogenic | -1.033 | Destabilizing | 0.995 | D | 0.867 | deleterious | None | None | None | None | I |
| A/G | 0.2559 | likely_benign | 0.2835 | benign | -0.927 | Destabilizing | 0.919 | D | 0.5 | neutral | D | 0.534214337 | None | None | I |
| A/H | 0.887 | likely_pathogenic | 0.8924 | pathogenic | -0.99 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | I |
| A/I | 0.8143 | likely_pathogenic | 0.8237 | pathogenic | -0.43 | Destabilizing | 0.995 | D | 0.831 | deleterious | None | None | None | None | I |
| A/K | 0.9294 | likely_pathogenic | 0.944 | pathogenic | -1.051 | Destabilizing | 0.991 | D | 0.761 | deleterious | None | None | None | None | I |
| A/L | 0.672 | likely_pathogenic | 0.6817 | pathogenic | -0.43 | Destabilizing | 0.968 | D | 0.675 | prob.neutral | None | None | None | None | I |
| A/M | 0.6218 | likely_pathogenic | 0.6273 | pathogenic | -0.349 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | I |
| A/N | 0.7739 | likely_pathogenic | 0.7889 | pathogenic | -0.713 | Destabilizing | 0.991 | D | 0.833 | deleterious | None | None | None | None | I |
| A/P | 0.9804 | likely_pathogenic | 0.9845 | pathogenic | -0.495 | Destabilizing | 0.994 | D | 0.835 | deleterious | D | 0.53236268 | None | None | I |
| A/Q | 0.763 | likely_pathogenic | 0.7758 | pathogenic | -0.926 | Destabilizing | 0.991 | D | 0.843 | deleterious | None | None | None | None | I |
| A/R | 0.8414 | likely_pathogenic | 0.8708 | pathogenic | -0.622 | Destabilizing | 0.991 | D | 0.84 | deleterious | None | None | None | None | I |
| A/S | 0.1296 | likely_benign | 0.1366 | benign | -1.039 | Destabilizing | 0.414 | N | 0.367 | neutral | N | 0.457636279 | None | None | I |
| A/T | 0.2138 | likely_benign | 0.2236 | benign | -1.034 | Destabilizing | 0.919 | D | 0.576 | neutral | D | 0.533520904 | None | None | I |
| A/V | 0.548 | ambiguous | 0.5721 | pathogenic | -0.495 | Destabilizing | 0.958 | D | 0.614 | neutral | N | 0.508636111 | None | None | I |
| A/W | 0.9746 | likely_pathogenic | 0.9766 | pathogenic | -1.269 | Destabilizing | 1.0 | D | 0.833 | deleterious | None | None | None | None | I |
| A/Y | 0.8906 | likely_pathogenic | 0.8975 | pathogenic | -0.901 | Destabilizing | 1.0 | D | 0.859 | deleterious | 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.