Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22819 | 68680;68681;68682 | chr2:178578060;178578059;178578058 | chr2:179442787;179442786;179442785 |
| N2AB | 21178 | 63757;63758;63759 | chr2:178578060;178578059;178578058 | chr2:179442787;179442786;179442785 |
| N2A | 20251 | 60976;60977;60978 | chr2:178578060;178578059;178578058 | chr2:179442787;179442786;179442785 |
| N2B | 13754 | 41485;41486;41487 | chr2:178578060;178578059;178578058 | chr2:179442787;179442786;179442785 |
| Novex-1 | 13879 | 41860;41861;41862 | chr2:178578060;178578059;178578058 | chr2:179442787;179442786;179442785 |
| Novex-2 | 13946 | 42061;42062;42063 | chr2:178578060;178578059;178578058 | chr2:179442787;179442786;179442785 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/L | rs878959858  |
None | 0.015 | N | 0.235 | 0.193 | 0.394079506076 | gnomAD-4.0.0 | 1.59252E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86048E-06 | 0 | 0 |
| M/T | rs770698117 |
-2.305 | 0.959 | N | 0.747 | 0.411 | 0.594339124078 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs770698117 |
-2.305 | 0.959 | N | 0.747 | 0.411 | 0.594339124078 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/T | rs770698117 |
-2.305 | 0.959 | N | 0.747 | 0.411 | 0.594339124078 | gnomAD-4.0.0 | 1.05385E-05 | None | None | None | None | N | None | 1.33526E-05 | 0 | None | 0 | 2.23444E-05 | None | 0 | 0 | 1.18698E-05 | 0 | 1.60179E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.5363 | ambiguous | 0.504 | ambiguous | -2.569 | Highly Destabilizing | 0.863 | D | 0.717 | prob.delet. | None | None | None | None | N |
| M/C | 0.7589 | likely_pathogenic | 0.7446 | pathogenic | -2.286 | Highly Destabilizing | 0.999 | D | 0.718 | prob.delet. | None | None | None | None | N |
| M/D | 0.9731 | likely_pathogenic | 0.9753 | pathogenic | -2.497 | Highly Destabilizing | 0.997 | D | 0.775 | deleterious | None | None | None | None | N |
| M/E | 0.8181 | likely_pathogenic | 0.8358 | pathogenic | -2.337 | Highly Destabilizing | 0.997 | D | 0.741 | deleterious | None | None | None | None | N |
| M/F | 0.4676 | ambiguous | 0.4166 | ambiguous | -1.032 | Destabilizing | 0.939 | D | 0.757 | deleterious | None | None | None | None | N |
| M/G | 0.8161 | likely_pathogenic | 0.8003 | pathogenic | -2.936 | Highly Destabilizing | 0.99 | D | 0.769 | deleterious | None | None | None | None | N |
| M/H | 0.7482 | likely_pathogenic | 0.761 | pathogenic | -2.413 | Highly Destabilizing | 0.999 | D | 0.713 | prob.delet. | None | None | None | None | N |
| M/I | 0.5943 | likely_pathogenic | 0.5993 | pathogenic | -1.515 | Destabilizing | 0.134 | N | 0.321 | neutral | N | 0.364770898 | None | None | N |
| M/K | 0.5445 | ambiguous | 0.5716 | pathogenic | -1.87 | Destabilizing | 0.986 | D | 0.759 | deleterious | N | 0.391301351 | None | None | N |
| M/L | 0.2526 | likely_benign | 0.231 | benign | -1.515 | Destabilizing | 0.015 | N | 0.235 | neutral | N | 0.409580468 | None | None | N |
| M/N | 0.7777 | likely_pathogenic | 0.7647 | pathogenic | -2.027 | Highly Destabilizing | 0.997 | D | 0.736 | prob.delet. | None | None | None | None | N |
| M/P | 0.9963 | likely_pathogenic | 0.9958 | pathogenic | -1.853 | Destabilizing | 0.997 | D | 0.736 | prob.delet. | None | None | None | None | N |
| M/Q | 0.4494 | ambiguous | 0.472 | ambiguous | -1.859 | Destabilizing | 0.997 | D | 0.769 | deleterious | None | None | None | None | N |
| M/R | 0.5222 | ambiguous | 0.5537 | ambiguous | -1.705 | Destabilizing | 0.996 | D | 0.765 | deleterious | N | 0.367693773 | None | None | N |
| M/S | 0.4565 | ambiguous | 0.4319 | ambiguous | -2.53 | Highly Destabilizing | 0.99 | D | 0.743 | deleterious | None | None | None | None | N |
| M/T | 0.2904 | likely_benign | 0.2755 | benign | -2.283 | Highly Destabilizing | 0.959 | D | 0.747 | deleterious | N | 0.396131168 | None | None | N |
| M/V | 0.2135 | likely_benign | 0.2043 | benign | -1.853 | Destabilizing | 0.509 | D | 0.525 | neutral | N | 0.386607608 | None | None | N |
| M/W | 0.8224 | likely_pathogenic | 0.8191 | pathogenic | -1.313 | Destabilizing | 0.999 | D | 0.717 | prob.delet. | None | None | None | None | N |
| M/Y | 0.7401 | likely_pathogenic | 0.7046 | pathogenic | -1.387 | Destabilizing | 0.997 | D | 0.757 | 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.