TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28169	84730;84731;84732	chr2:178561627;178561626;178561625	chr2:179426354;179426353;179426352
N2AB	26528	79807;79808;79809	chr2:178561627;178561626;178561625	chr2:179426354;179426353;179426352
N2A	25601	77026;77027;77028	chr2:178561627;178561626;178561625	chr2:179426354;179426353;179426352
N2B	19104	57535;57536;57537	chr2:178561627;178561626;178561625	chr2:179426354;179426353;179426352
Novex-1	19229	57910;57911;57912	chr2:178561627;178561626;178561625	chr2:179426354;179426353;179426352
Novex-2	19296	58111;58112;58113	chr2:178561627;178561626;178561625	chr2:179426354;179426353;179426352
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-93
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4275
• 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
S/A	None	None	0.001	N	0.071	0.094	0.126345400529	gnomAD-4.0.0	3.19103E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72928E-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
S/A	0.0765	likely_benign	0.0819	benign	-0.71	Destabilizing	0.001	N	0.071	neutral	N	0.500474618	None	None	N
S/C	0.1062	likely_benign	0.1134	benign	-0.444	Destabilizing	0.987	D	0.358	neutral	N	0.476665611	None	None	N
S/D	0.2695	likely_benign	0.2585	benign	-0.272	Destabilizing	0.39	N	0.209	neutral	None	None	None	None	N
S/E	0.3772	ambiguous	0.3777	ambiguous	-0.345	Destabilizing	0.002	N	0.055	neutral	None	None	None	None	N
S/F	0.1753	likely_benign	0.1863	benign	-1.264	Destabilizing	0.326	N	0.407	neutral	N	0.483248977	None	None	N
S/G	0.0896	likely_benign	0.0899	benign	-0.843	Destabilizing	0.209	N	0.235	neutral	None	None	None	None	N
S/H	0.2713	likely_benign	0.2645	benign	-1.418	Destabilizing	0.818	D	0.365	neutral	None	None	None	None	N
S/I	0.2223	likely_benign	0.2235	benign	-0.474	Destabilizing	0.39	N	0.374	neutral	None	None	None	None	N
S/K	0.5858	likely_pathogenic	0.5705	pathogenic	-0.59	Destabilizing	0.39	N	0.21	neutral	None	None	None	None	N
S/L	0.1088	likely_benign	0.1152	benign	-0.474	Destabilizing	0.209	N	0.318	neutral	None	None	None	None	N
S/M	0.1549	likely_benign	0.16	benign	0.029	Stabilizing	0.901	D	0.366	neutral	None	None	None	None	N
S/N	0.0869	likely_benign	0.082	benign	-0.39	Destabilizing	0.561	D	0.26	neutral	None	None	None	None	N
S/P	0.7604	likely_pathogenic	0.8246	pathogenic	-0.525	Destabilizing	0.662	D	0.435	neutral	N	0.482995487	None	None	N
S/Q	0.3788	ambiguous	0.37	ambiguous	-0.737	Destabilizing	0.39	N	0.328	neutral	None	None	None	None	N
S/R	0.5605	ambiguous	0.5417	ambiguous	-0.354	Destabilizing	0.561	D	0.433	neutral	None	None	None	None	N
S/T	0.0762	likely_benign	0.0757	benign	-0.499	Destabilizing	0.013	N	0.096	neutral	N	0.448346713	None	None	N
S/V	0.1966	likely_benign	0.2046	benign	-0.525	Destabilizing	0.004	N	0.267	neutral	None	None	None	None	N
S/W	0.3195	likely_benign	0.3347	benign	-1.185	Destabilizing	0.991	D	0.348	neutral	None	None	None	None	N
S/Y	0.1349	likely_benign	0.1384	benign	-0.928	Destabilizing	0.005	N	0.165	neutral	N	0.489430905	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.