TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30196	90811;90812;90813	chr2:178552314;178552313;178552312	chr2:179417041;179417040;179417039
N2AB	28555	85888;85889;85890	chr2:178552314;178552313;178552312	chr2:179417041;179417040;179417039
N2A	27628	83107;83108;83109	chr2:178552314;178552313;178552312	chr2:179417041;179417040;179417039
N2B	21131	63616;63617;63618	chr2:178552314;178552313;178552312	chr2:179417041;179417040;179417039
Novex-1	21256	63991;63992;63993	chr2:178552314;178552313;178552312	chr2:179417041;179417040;179417039
Novex-2	21323	64192;64193;64194	chr2:178552314;178552313;178552312	chr2:179417041;179417040;179417039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-148
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.8841
• 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
K/T	None	None	1.0	N	0.667	0.454	0.302793454619	gnomAD-4.0.0	1.59921E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.03472E-05

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
K/A	0.6685	likely_pathogenic	0.5868	pathogenic	0.051	Stabilizing	0.999	D	0.655	neutral	None	None	None	None	N
K/C	0.9272	likely_pathogenic	0.8915	pathogenic	-0.401	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/D	0.8983	likely_pathogenic	0.8568	pathogenic	-0.197	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/E	0.4972	ambiguous	0.4246	ambiguous	-0.203	Destabilizing	0.999	D	0.665	neutral	N	0.482085566	None	None	N
K/F	0.943	likely_pathogenic	0.9171	pathogenic	-0.274	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
K/G	0.8325	likely_pathogenic	0.7728	pathogenic	-0.088	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
K/H	0.6501	likely_pathogenic	0.5709	pathogenic	-0.204	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/I	0.5921	likely_pathogenic	0.5261	ambiguous	0.335	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
K/L	0.6132	likely_pathogenic	0.5608	ambiguous	0.335	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	N
K/M	0.4648	ambiguous	0.4097	ambiguous	-0.059	Destabilizing	1.0	D	0.689	prob.neutral	N	0.46704842	None	None	N
K/N	0.8228	likely_pathogenic	0.7402	pathogenic	0.064	Stabilizing	1.0	D	0.735	prob.delet.	N	0.47117625	None	None	N
K/P	0.7618	likely_pathogenic	0.7053	pathogenic	0.265	Stabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
K/Q	0.3056	likely_benign	0.2776	benign	-0.062	Destabilizing	1.0	D	0.725	prob.delet.	N	0.459059476	None	None	N
K/R	0.1008	likely_benign	0.0985	benign	-0.06	Destabilizing	0.999	D	0.624	neutral	N	0.450242507	None	None	N
K/S	0.8258	likely_pathogenic	0.752	pathogenic	-0.306	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
K/T	0.4985	ambiguous	0.4229	ambiguous	-0.189	Destabilizing	1.0	D	0.667	neutral	N	0.507117297	None	None	N
K/V	0.5743	likely_pathogenic	0.5279	ambiguous	0.265	Stabilizing	1.0	D	0.67	neutral	None	None	None	None	N
K/W	0.9061	likely_pathogenic	0.8731	pathogenic	-0.383	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/Y	0.8521	likely_pathogenic	0.793	pathogenic	-0.021	Destabilizing	1.0	D	0.692	prob.neutral	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.