TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28870	86833;86834;86835	chr2:178559524;178559523;178559522	chr2:179424251;179424250;179424249
N2AB	27229	81910;81911;81912	chr2:178559524;178559523;178559522	chr2:179424251;179424250;179424249
N2A	26302	79129;79130;79131	chr2:178559524;178559523;178559522	chr2:179424251;179424250;179424249
N2B	19805	59638;59639;59640	chr2:178559524;178559523;178559522	chr2:179424251;179424250;179424249
Novex-1	19930	60013;60014;60015	chr2:178559524;178559523;178559522	chr2:179424251;179424250;179424249
Novex-2	19997	60214;60215;60216	chr2:178559524;178559523;178559522	chr2:179424251;179424250;179424249
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: Fn3-98
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.885
• 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/A	None	None	0.939	N	0.571	0.347	0.434384183301	gnomAD-4.0.0	2.7369E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.598E-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
E/A	0.1441	likely_benign	0.1395	benign	-0.012	Destabilizing	0.939	D	0.571	neutral	N	0.481077994	None	None	I
E/C	0.7968	likely_pathogenic	0.7898	pathogenic	-0.041	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	I
E/D	0.1184	likely_benign	0.1107	benign	-0.177	Destabilizing	0.02	N	0.216	neutral	N	0.467226049	None	None	I
E/F	0.7294	likely_pathogenic	0.7205	pathogenic	-0.073	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	I
E/G	0.1563	likely_benign	0.1531	benign	-0.14	Destabilizing	0.939	D	0.471	neutral	N	0.47984863	None	None	I
E/H	0.4778	ambiguous	0.4507	ambiguous	0.425	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	I
E/I	0.2723	likely_benign	0.2676	benign	0.269	Stabilizing	0.993	D	0.676	prob.neutral	None	None	None	None	I
E/K	0.1407	likely_benign	0.1304	benign	0.471	Stabilizing	0.939	D	0.587	neutral	N	0.456680982	None	None	I
E/L	0.3219	likely_benign	0.3138	benign	0.269	Stabilizing	0.993	D	0.671	neutral	None	None	None	None	I
E/M	0.4191	ambiguous	0.4065	ambiguous	0.106	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	I
E/N	0.2482	likely_benign	0.2341	benign	0.32	Stabilizing	0.973	D	0.589	neutral	None	None	None	None	I
E/P	0.5174	ambiguous	0.5205	ambiguous	0.194	Stabilizing	0.993	D	0.617	neutral	None	None	None	None	I
E/Q	0.1415	likely_benign	0.1333	benign	0.322	Stabilizing	0.991	D	0.581	neutral	N	0.508958028	None	None	I
E/R	0.259	likely_benign	0.247	benign	0.669	Stabilizing	0.993	D	0.658	neutral	None	None	None	None	I
E/S	0.1906	likely_benign	0.18	benign	0.144	Stabilizing	0.953	D	0.588	neutral	None	None	None	None	I
E/T	0.2162	likely_benign	0.2037	benign	0.251	Stabilizing	0.993	D	0.543	neutral	None	None	None	None	I
E/V	0.1658	likely_benign	0.1668	benign	0.194	Stabilizing	0.991	D	0.622	neutral	N	0.487486678	None	None	I
E/W	0.8791	likely_pathogenic	0.87	pathogenic	-0.029	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
E/Y	0.6145	likely_pathogenic	0.5883	pathogenic	0.155	Stabilizing	0.999	D	0.622	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.