TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29472	88639;88640;88641	chr2:178555045;178555044;178555043	chr2:179419772;179419771;179419770
N2AB	27831	83716;83717;83718	chr2:178555045;178555044;178555043	chr2:179419772;179419771;179419770
N2A	26904	80935;80936;80937	chr2:178555045;178555044;178555043	chr2:179419772;179419771;179419770
N2B	20407	61444;61445;61446	chr2:178555045;178555044;178555043	chr2:179419772;179419771;179419770
Novex-1	20532	61819;61820;61821	chr2:178555045;178555044;178555043	chr2:179419772;179419771;179419770
Novex-2	20599	62020;62021;62022	chr2:178555045;178555044;178555043	chr2:179419772;179419771;179419770
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-146
• Domain position: 29
• Structural Position: 46
• Q(SASA): 0.2063
• 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
I/T	rs1700836863	None	0.989	N	0.771	0.693	0.778047502339	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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
I/A	0.2173	likely_benign	0.2021	benign	-2.162	Highly Destabilizing	0.992	D	0.692	prob.neutral	None	None	None	None	N
I/C	0.7633	likely_pathogenic	0.7726	pathogenic	-1.401	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
I/D	0.952	likely_pathogenic	0.9458	pathogenic	-1.935	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
I/E	0.8535	likely_pathogenic	0.8393	pathogenic	-1.826	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
I/F	0.3525	ambiguous	0.3298	benign	-1.353	Destabilizing	0.998	D	0.725	prob.delet.	D	0.528486018	None	None	N
I/G	0.8052	likely_pathogenic	0.79	pathogenic	-2.605	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
I/H	0.8694	likely_pathogenic	0.8558	pathogenic	-1.843	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/K	0.7059	likely_pathogenic	0.6697	pathogenic	-1.69	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
I/L	0.2175	likely_benign	0.2065	benign	-0.952	Destabilizing	0.889	D	0.472	neutral	N	0.517748949	None	None	N
I/M	0.1258	likely_benign	0.1176	benign	-0.77	Destabilizing	0.998	D	0.691	prob.neutral	D	0.538068293	None	None	N
I/N	0.7395	likely_pathogenic	0.7308	pathogenic	-1.682	Destabilizing	0.999	D	0.854	deleterious	N	0.516178345	None	None	N
I/P	0.8519	likely_pathogenic	0.8306	pathogenic	-1.329	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
I/Q	0.7561	likely_pathogenic	0.739	pathogenic	-1.719	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/R	0.5987	likely_pathogenic	0.5528	ambiguous	-1.189	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/S	0.4225	ambiguous	0.4082	ambiguous	-2.344	Highly Destabilizing	0.998	D	0.833	deleterious	N	0.515924855	None	None	N
I/T	0.1337	likely_benign	0.1294	benign	-2.098	Highly Destabilizing	0.989	D	0.771	deleterious	N	0.492958755	None	None	N
I/V	0.0622	likely_benign	0.0636	benign	-1.329	Destabilizing	0.333	N	0.205	neutral	N	0.447450997	None	None	N
I/W	0.8984	likely_pathogenic	0.8761	pathogenic	-1.552	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/Y	0.79	likely_pathogenic	0.7664	pathogenic	-1.316	Destabilizing	1.0	D	0.737	prob.delet.	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.