TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28265	85018;85019;85020	chr2:178561339;178561338;178561337	chr2:179426066;179426065;179426064
N2AB	26624	80095;80096;80097	chr2:178561339;178561338;178561337	chr2:179426066;179426065;179426064
N2A	25697	77314;77315;77316	chr2:178561339;178561338;178561337	chr2:179426066;179426065;179426064
N2B	19200	57823;57824;57825	chr2:178561339;178561338;178561337	chr2:179426066;179426065;179426064
Novex-1	19325	58198;58199;58200	chr2:178561339;178561338;178561337	chr2:179426066;179426065;179426064
Novex-2	19392	58399;58400;58401	chr2:178561339;178561338;178561337	chr2:179426066;179426065;179426064
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: Fn3-94
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.248
• 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/K	rs376874908	None	1.0	N	0.775	0.479	None	gnomAD-4.0.0	1.5912E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85809E-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	0.3881	ambiguous	0.4149	ambiguous	-0.841	Destabilizing	0.999	D	0.48	neutral	N	0.492403236	None	None	N
T/C	0.7621	likely_pathogenic	0.7626	pathogenic	-0.821	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
T/D	0.7322	likely_pathogenic	0.7244	pathogenic	-1.315	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
T/E	0.8512	likely_pathogenic	0.8555	pathogenic	-1.264	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/F	0.7822	likely_pathogenic	0.796	pathogenic	-0.825	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
T/G	0.3845	ambiguous	0.3879	ambiguous	-1.136	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
T/H	0.5948	likely_pathogenic	0.5824	pathogenic	-1.426	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
T/I	0.8665	likely_pathogenic	0.8881	pathogenic	-0.131	Destabilizing	1.0	D	0.767	deleterious	D	0.534652134	None	None	N
T/K	0.6271	likely_pathogenic	0.6093	pathogenic	-0.92	Destabilizing	1.0	D	0.775	deleterious	N	0.485566381	None	None	N
T/L	0.4339	ambiguous	0.4633	ambiguous	-0.131	Destabilizing	0.999	D	0.653	neutral	None	None	None	None	N
T/M	0.3279	likely_benign	0.3622	ambiguous	0.124	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
T/N	0.2503	likely_benign	0.2512	benign	-1.18	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/P	0.8672	likely_pathogenic	0.876	pathogenic	-0.336	Destabilizing	1.0	D	0.749	deleterious	D	0.534652134	None	None	N
T/Q	0.5919	likely_pathogenic	0.5855	pathogenic	-1.331	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
T/R	0.5714	likely_pathogenic	0.5649	pathogenic	-0.682	Destabilizing	1.0	D	0.756	deleterious	N	0.48456565	None	None	N
T/S	0.1499	likely_benign	0.1502	benign	-1.321	Destabilizing	0.999	D	0.507	neutral	N	0.48992955	None	None	N
T/V	0.7434	likely_pathogenic	0.7683	pathogenic	-0.336	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	N
T/W	0.9284	likely_pathogenic	0.9341	pathogenic	-0.837	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
T/Y	0.784	likely_pathogenic	0.7874	pathogenic	-0.543	Destabilizing	1.0	D	0.771	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.