Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17223 | 51892;51893;51894 | chr2:178609756;178609755;178609754 | chr2:179474483;179474482;179474481 |
| N2AB | 15582 | 46969;46970;46971 | chr2:178609756;178609755;178609754 | chr2:179474483;179474482;179474481 |
| N2A | 14655 | 44188;44189;44190 | chr2:178609756;178609755;178609754 | chr2:179474483;179474482;179474481 |
| N2B | 8158 | 24697;24698;24699 | chr2:178609756;178609755;178609754 | chr2:179474483;179474482;179474481 |
| Novex-1 | 8283 | 25072;25073;25074 | chr2:178609756;178609755;178609754 | chr2:179474483;179474482;179474481 |
| Novex-2 | 8350 | 25273;25274;25275 | chr2:178609756;178609755;178609754 | chr2:179474483;179474482;179474481 |
| 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/Q | rs142395261  |
-1.074 | 0.996 | N | 0.694 | 0.287 | None | gnomAD-2.1.1 | 2.5E-05 | None | None | None | None | I | None | 1.65549E-04 | 8.49E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/Q | rs142395261 |
-1.074 | 0.996 | N | 0.694 | 0.287 | None | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | I | None | 2.65662E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78927E-04 |
| R/Q | rs142395261 |
-1.074 | 0.996 | N | 0.694 | 0.287 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs142395261 |
-1.074 | 0.996 | N | 0.694 | 0.287 | None | gnomAD-4.0.0 | 1.79828E-05 | None | None | None | None | I | None | 2.26872E-04 | 3.33589E-05 | None | 0 | 0 | None | 0 | 0 | 6.78493E-06 | 0 | 3.20431E-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 | 0.7153 | likely_pathogenic | 0.6718 | pathogenic | -1.577 | Destabilizing | 0.931 | D | 0.612 | neutral | None | None | None | None | I |
| R/C | 0.2817 | likely_benign | 0.2429 | benign | -1.757 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/D | 0.9797 | likely_pathogenic | 0.9783 | pathogenic | -0.953 | Destabilizing | 0.996 | D | 0.652 | neutral | None | None | None | None | I |
| R/E | 0.8384 | likely_pathogenic | 0.8036 | pathogenic | -0.771 | Destabilizing | 0.985 | D | 0.665 | neutral | None | None | None | None | I |
| R/F | 0.7398 | likely_pathogenic | 0.7309 | pathogenic | -0.997 | Destabilizing | 0.999 | D | 0.725 | prob.delet. | None | None | None | None | I |
| R/G | 0.7824 | likely_pathogenic | 0.757 | pathogenic | -1.894 | Destabilizing | 0.992 | D | 0.601 | neutral | D | 0.525987946 | None | None | I |
| R/H | 0.3213 | likely_benign | 0.289 | benign | -1.93 | Destabilizing | 0.999 | D | 0.652 | neutral | None | None | None | None | I |
| R/I | 0.5333 | ambiguous | 0.462 | ambiguous | -0.683 | Destabilizing | 0.998 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/K | 0.1828 | likely_benign | 0.1588 | benign | -1.482 | Destabilizing | 0.271 | N | 0.311 | neutral | None | None | None | None | I |
| R/L | 0.4965 | ambiguous | 0.5159 | ambiguous | -0.683 | Destabilizing | 0.996 | D | 0.599 | neutral | N | 0.469255644 | None | None | I |
| R/M | 0.5024 | ambiguous | 0.4423 | ambiguous | -1.186 | Destabilizing | 1.0 | D | 0.644 | neutral | None | None | None | None | I |
| R/N | 0.9304 | likely_pathogenic | 0.9307 | pathogenic | -1.301 | Destabilizing | 0.985 | D | 0.645 | neutral | None | None | None | None | I |
| R/P | 0.9967 | likely_pathogenic | 0.9967 | pathogenic | -0.967 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | D | 0.526241435 | None | None | I |
| R/Q | 0.2677 | likely_benign | 0.2214 | benign | -1.18 | Destabilizing | 0.996 | D | 0.694 | prob.neutral | N | 0.480101289 | None | None | I |
| R/S | 0.7907 | likely_pathogenic | 0.7672 | pathogenic | -2.03 | Highly Destabilizing | 0.719 | D | 0.433 | neutral | None | None | None | None | I |
| R/T | 0.5816 | likely_pathogenic | 0.5307 | ambiguous | -1.657 | Destabilizing | 0.985 | D | 0.584 | neutral | None | None | None | None | I |
| R/V | 0.594 | likely_pathogenic | 0.5408 | ambiguous | -0.967 | Destabilizing | 0.998 | D | 0.691 | prob.neutral | None | None | None | None | I |
| R/W | 0.4776 | ambiguous | 0.4551 | ambiguous | -0.66 | Destabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | I |
| R/Y | 0.6674 | likely_pathogenic | 0.6716 | pathogenic | -0.416 | Destabilizing | 0.999 | D | 0.697 | 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.