TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24387	73384;73385;73386	chr2:178572973;178572972;178572971	chr2:179437700;179437699;179437698
N2AB	22746	68461;68462;68463	chr2:178572973;178572972;178572971	chr2:179437700;179437699;179437698
N2A	21819	65680;65681;65682	chr2:178572973;178572972;178572971	chr2:179437700;179437699;179437698
N2B	15322	46189;46190;46191	chr2:178572973;178572972;178572971	chr2:179437700;179437699;179437698
Novex-1	15447	46564;46565;46566	chr2:178572973;178572972;178572971	chr2:179437700;179437699;179437698
Novex-2	15514	46765;46766;46767	chr2:178572973;178572972;178572971	chr2:179437700;179437699;179437698
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-65
• Domain position: 65
• Structural Position: 94
• Q(SASA): 0.5788
• 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
T/I	None	None	0.997	N	0.743	0.415	0.491112125781	gnomAD-4.0.0	1.59265E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86004E-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
T/A	0.0764	likely_benign	0.0793	benign	-0.547	Destabilizing	0.977	D	0.448	neutral	N	0.48585587	None	None	N
T/C	0.3048	likely_benign	0.3182	benign	-0.369	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	N
T/D	0.2869	likely_benign	0.3248	benign	0.531	Stabilizing	0.995	D	0.671	neutral	None	None	None	None	N
T/E	0.209	likely_benign	0.2335	benign	0.475	Stabilizing	0.966	D	0.645	neutral	None	None	None	None	N
T/F	0.2413	likely_benign	0.2556	benign	-1.042	Destabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
T/G	0.1719	likely_benign	0.192	benign	-0.685	Destabilizing	0.995	D	0.643	neutral	None	None	None	None	N
T/H	0.1934	likely_benign	0.2091	benign	-0.955	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/I	0.1357	likely_benign	0.1445	benign	-0.298	Destabilizing	0.997	D	0.743	deleterious	N	0.48564206	None	None	N
T/K	0.1291	likely_benign	0.145	benign	-0.256	Destabilizing	0.289	N	0.315	neutral	None	None	None	None	N
T/L	0.0869	likely_benign	0.0896	benign	-0.298	Destabilizing	0.983	D	0.617	neutral	None	None	None	None	N
T/M	0.0913	likely_benign	0.0963	benign	-0.136	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
T/N	0.1056	likely_benign	0.1186	benign	-0.125	Destabilizing	0.993	D	0.61	neutral	N	0.472004349	None	None	N
T/P	0.0863	likely_benign	0.0965	benign	-0.353	Destabilizing	0.997	D	0.743	deleterious	N	0.51925238	None	None	N
T/Q	0.1658	likely_benign	0.1817	benign	-0.293	Destabilizing	0.995	D	0.74	deleterious	None	None	None	None	N
T/R	0.1299	likely_benign	0.141	benign	-0.066	Destabilizing	0.99	D	0.67	neutral	None	None	None	None	N
T/S	0.0924	likely_benign	0.1001	benign	-0.419	Destabilizing	0.977	D	0.417	neutral	N	0.482136786	None	None	N
T/V	0.1107	likely_benign	0.118	benign	-0.353	Destabilizing	0.991	D	0.517	neutral	None	None	None	None	N
T/W	0.5499	ambiguous	0.5821	pathogenic	-1.011	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/Y	0.2729	likely_benign	0.2974	benign	-0.724	Destabilizing	0.999	D	0.744	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.