TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28302	85129;85130;85131	chr2:178561228;178561227;178561226	chr2:179425955;179425954;179425953
N2AB	26661	80206;80207;80208	chr2:178561228;178561227;178561226	chr2:179425955;179425954;179425953
N2A	25734	77425;77426;77427	chr2:178561228;178561227;178561226	chr2:179425955;179425954;179425953
N2B	19237	57934;57935;57936	chr2:178561228;178561227;178561226	chr2:179425955;179425954;179425953
Novex-1	19362	58309;58310;58311	chr2:178561228;178561227;178561226	chr2:179425955;179425954;179425953
Novex-2	19429	58510;58511;58512	chr2:178561228;178561227;178561226	chr2:179425955;179425954;179425953
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-94
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.1929
• Predicted PPI site: N

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
C/S	None	None	0.698	N	0.559	0.445	0.569844293628	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
C/A	0.6149	likely_pathogenic	0.5813	pathogenic	-1.797	Destabilizing	0.019	N	0.261	neutral	None	None	None	None	N
C/D	0.9939	likely_pathogenic	0.9932	pathogenic	-0.596	Destabilizing	0.978	D	0.756	deleterious	None	None	None	None	N
C/E	0.9958	likely_pathogenic	0.9957	pathogenic	-0.416	Destabilizing	0.956	D	0.761	deleterious	None	None	None	None	N
C/F	0.83	likely_pathogenic	0.8506	pathogenic	-1.115	Destabilizing	0.97	D	0.758	deleterious	N	0.469692809	None	None	N
C/G	0.6316	likely_pathogenic	0.5598	ambiguous	-2.147	Highly Destabilizing	0.698	D	0.669	neutral	N	0.491319464	None	None	N
C/H	0.9747	likely_pathogenic	0.9783	pathogenic	-2.114	Highly Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
C/I	0.8562	likely_pathogenic	0.8684	pathogenic	-0.863	Destabilizing	0.956	D	0.661	neutral	None	None	None	None	N
C/K	0.9975	likely_pathogenic	0.9975	pathogenic	-0.906	Destabilizing	0.956	D	0.748	deleterious	None	None	None	None	N
C/L	0.8755	likely_pathogenic	0.8818	pathogenic	-0.863	Destabilizing	0.754	D	0.54	neutral	None	None	None	None	N
C/M	0.9127	likely_pathogenic	0.9191	pathogenic	0.248	Stabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
C/N	0.9615	likely_pathogenic	0.9603	pathogenic	-1.257	Destabilizing	0.978	D	0.788	deleterious	None	None	None	None	N
C/P	0.9965	likely_pathogenic	0.9959	pathogenic	-1.151	Destabilizing	0.978	D	0.78	deleterious	None	None	None	None	N
C/Q	0.9841	likely_pathogenic	0.9842	pathogenic	-0.933	Destabilizing	0.978	D	0.782	deleterious	None	None	None	None	N
C/R	0.9817	likely_pathogenic	0.9823	pathogenic	-1.055	Destabilizing	0.97	D	0.785	deleterious	N	0.504686778	None	None	N
C/S	0.6763	likely_pathogenic	0.6381	pathogenic	-1.734	Destabilizing	0.698	D	0.559	neutral	N	0.490305506	None	None	N
C/T	0.8353	likely_pathogenic	0.8094	pathogenic	-1.354	Destabilizing	0.86	D	0.612	neutral	None	None	None	None	N
C/V	0.7113	likely_pathogenic	0.7121	pathogenic	-1.151	Destabilizing	0.754	D	0.559	neutral	None	None	None	None	N
C/W	0.9646	likely_pathogenic	0.9731	pathogenic	-1.246	Destabilizing	0.997	D	0.735	prob.delet.	N	0.518831468	None	None	N
C/Y	0.9043	likely_pathogenic	0.9207	pathogenic	-1.171	Destabilizing	0.99	D	0.76	deleterious	N	0.490812485	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.