TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13916	41971;41972;41973	chr2:178635578;178635577;178635576	chr2:179500305;179500304;179500303
N2AB	12275	37048;37049;37050	chr2:178635578;178635577;178635576	chr2:179500305;179500304;179500303
N2A	11348	34267;34268;34269	chr2:178635578;178635577;178635576	chr2:179500305;179500304;179500303
N2B	4851	14776;14777;14778	chr2:178635578;178635577;178635576	chr2:179500305;179500304;179500303
Novex-1	4976	15151;15152;15153	chr2:178635578;178635577;178635576	chr2:179500305;179500304;179500303
Novex-2	5043	15352;15353;15354	chr2:178635578;178635577;178635576	chr2:179500305;179500304;179500303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-89
• Domain position: 41
• Structural Position: 71
• Q(SASA): 0.5885
• Predicted PPI site: I

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
E/D	None	None	0.034	N	0.312	0.021	0.0806252709748	gnomAD-4.0.0	1.64186E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.92589E-05	0	0	0	0
E/K	None	None	0.132	N	0.334	0.229	0.173771789658	gnomAD-4.0.0	6.93514E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.0831E-07	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
E/A	0.2002	likely_benign	0.1991	benign	-0.041	Destabilizing	0.919	D	0.559	neutral	N	0.476357861	None	None	I
E/C	0.914	likely_pathogenic	0.92	pathogenic	-0.202	Destabilizing	0.999	D	0.721	deleterious	None	None	None	None	I
E/D	0.1802	likely_benign	0.2062	benign	-0.225	Destabilizing	0.034	N	0.312	neutral	N	0.446322138	None	None	I
E/F	0.7831	likely_pathogenic	0.7847	pathogenic	-0.12	Destabilizing	0.997	D	0.555	neutral	None	None	None	None	I
E/G	0.2667	likely_benign	0.2558	benign	-0.153	Destabilizing	0.919	D	0.454	neutral	N	0.428188785	None	None	I
E/H	0.71	likely_pathogenic	0.6975	pathogenic	0.473	Stabilizing	0.997	D	0.479	neutral	None	None	None	None	I
E/I	0.3717	ambiguous	0.3743	ambiguous	0.198	Stabilizing	0.997	D	0.578	neutral	None	None	None	None	I
E/K	0.2894	likely_benign	0.2454	benign	0.318	Stabilizing	0.132	N	0.334	neutral	N	0.448136185	None	None	I
E/L	0.4609	ambiguous	0.4814	ambiguous	0.198	Stabilizing	0.991	D	0.533	neutral	None	None	None	None	I
E/M	0.5105	ambiguous	0.5058	ambiguous	-0.035	Destabilizing	0.999	D	0.526	neutral	None	None	None	None	I
E/N	0.3834	ambiguous	0.3903	ambiguous	0.195	Stabilizing	0.938	D	0.582	neutral	None	None	None	None	I
E/P	0.7749	likely_pathogenic	0.8209	pathogenic	0.136	Stabilizing	0.997	D	0.551	neutral	None	None	None	None	I
E/Q	0.2271	likely_benign	0.2165	benign	0.194	Stabilizing	0.919	D	0.565	neutral	N	0.479591501	None	None	I
E/R	0.5231	ambiguous	0.4856	ambiguous	0.561	Stabilizing	0.883	D	0.552	neutral	None	None	None	None	I
E/S	0.2906	likely_benign	0.2898	benign	0.015	Stabilizing	0.938	D	0.56	neutral	None	None	None	None	I
E/T	0.263	likely_benign	0.2606	benign	0.109	Stabilizing	0.968	D	0.522	neutral	None	None	None	None	I
E/V	0.2304	likely_benign	0.2272	benign	0.136	Stabilizing	0.988	D	0.445	neutral	N	0.451650714	None	None	I
E/W	0.958	likely_pathogenic	0.9584	pathogenic	-0.087	Destabilizing	0.999	D	0.729	deleterious	None	None	None	None	I
E/Y	0.7418	likely_pathogenic	0.7468	pathogenic	0.097	Stabilizing	0.997	D	0.502	neutral	None	None	None	None	I

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.