TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16673	50242;50243;50244	chr2:178612508;178612507;178612506	chr2:179477235;179477234;179477233
N2AB	15032	45319;45320;45321	chr2:178612508;178612507;178612506	chr2:179477235;179477234;179477233
N2A	14105	42538;42539;42540	chr2:178612508;178612507;178612506	chr2:179477235;179477234;179477233
N2B	7608	23047;23048;23049	chr2:178612508;178612507;178612506	chr2:179477235;179477234;179477233
Novex-1	7733	23422;23423;23424	chr2:178612508;178612507;178612506	chr2:179477235;179477234;179477233
Novex-2	7800	23623;23624;23625	chr2:178612508;178612507;178612506	chr2:179477235;179477234;179477233
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-9
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.2484
• 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/R	rs373889292	None	1.0	N	0.819	0.484	None	gnomAD-4.0.0	3.42471E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49959E-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	0.1861	likely_benign	0.2955	benign	-0.874	Destabilizing	0.999	D	0.547	neutral	N	0.484372876	None	None	N
T/C	0.7405	likely_pathogenic	0.7575	pathogenic	-0.499	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/D	0.6963	likely_pathogenic	0.8359	pathogenic	-1.13	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/E	0.5192	ambiguous	0.77	pathogenic	-0.956	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
T/F	0.5918	likely_pathogenic	0.7863	pathogenic	-0.518	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
T/G	0.4841	ambiguous	0.5265	ambiguous	-1.279	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
T/H	0.5889	likely_pathogenic	0.7479	pathogenic	-1.457	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
T/I	0.4072	ambiguous	0.6711	pathogenic	0.178	Stabilizing	1.0	D	0.803	deleterious	N	0.47131187	None	None	N
T/K	0.452	ambiguous	0.7911	pathogenic	-0.597	Destabilizing	1.0	D	0.799	deleterious	N	0.460347916	None	None	N
T/L	0.2279	likely_benign	0.3844	ambiguous	0.178	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
T/M	0.1415	likely_benign	0.2323	benign	0.159	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
T/N	0.2798	likely_benign	0.3463	ambiguous	-1.152	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
T/P	0.6605	likely_pathogenic	0.8344	pathogenic	-0.141	Destabilizing	1.0	D	0.815	deleterious	D	0.57008795	None	None	N
T/Q	0.3984	ambiguous	0.6042	pathogenic	-0.923	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
T/R	0.4107	ambiguous	0.7762	pathogenic	-0.775	Destabilizing	1.0	D	0.819	deleterious	N	0.484071243	None	None	N
T/S	0.2453	likely_benign	0.2792	benign	-1.343	Destabilizing	0.999	D	0.52	neutral	N	0.466448598	None	None	N
T/V	0.308	likely_benign	0.4569	ambiguous	-0.141	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
T/W	0.8576	likely_pathogenic	0.9469	pathogenic	-0.741	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
T/Y	0.6496	likely_pathogenic	0.8236	pathogenic	-0.354	Destabilizing	1.0	D	0.848	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.