TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17183	51772;51773;51774	chr2:178609876;178609875;178609874	chr2:179474603;179474602;179474601
N2AB	15542	46849;46850;46851	chr2:178609876;178609875;178609874	chr2:179474603;179474602;179474601
N2A	14615	44068;44069;44070	chr2:178609876;178609875;178609874	chr2:179474603;179474602;179474601
N2B	8118	24577;24578;24579	chr2:178609876;178609875;178609874	chr2:179474603;179474602;179474601
Novex-1	8243	24952;24953;24954	chr2:178609876;178609875;178609874	chr2:179474603;179474602;179474601
Novex-2	8310	25153;25154;25155	chr2:178609876;178609875;178609874	chr2:179474603;179474602;179474601
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-13
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1321
• 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	rs757000767	-3.228	0.939	N	0.678	0.336	0.615520507219	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
I/T	rs757000767	-3.228	0.939	N	0.678	0.336	0.615520507219	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	2.42E-05	6.57E-05	0	0	0	None	0	0	0	0	0
I/T	rs757000767	-3.228	0.939	N	0.678	0.336	0.615520507219	gnomAD-4.0.0	3.8477E-06	None	None	None	None	N	None	3.38914E-05	1.69624E-05	None	0	0	None	0	0	0	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	0.9039	likely_pathogenic	0.8825	pathogenic	-2.921	Highly Destabilizing	0.91	D	0.677	prob.neutral	None	None	None	None	N
I/C	0.8961	likely_pathogenic	0.879	pathogenic	-2.096	Highly Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
I/D	0.9844	likely_pathogenic	0.9787	pathogenic	-3.494	Highly Destabilizing	0.998	D	0.775	deleterious	None	None	None	None	N
I/E	0.9528	likely_pathogenic	0.9409	pathogenic	-3.285	Highly Destabilizing	0.993	D	0.749	deleterious	None	None	None	None	N
I/F	0.4524	ambiguous	0.4129	ambiguous	-1.804	Destabilizing	0.982	D	0.697	prob.neutral	N	0.521135105	None	None	N
I/G	0.9817	likely_pathogenic	0.9739	pathogenic	-3.412	Highly Destabilizing	0.993	D	0.743	deleterious	None	None	None	None	N
I/H	0.8568	likely_pathogenic	0.8388	pathogenic	-2.816	Highly Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
I/K	0.9166	likely_pathogenic	0.8953	pathogenic	-2.435	Highly Destabilizing	0.993	D	0.747	deleterious	None	None	None	None	N
I/L	0.2851	likely_benign	0.2683	benign	-1.486	Destabilizing	0.58	D	0.473	neutral	N	0.489292045	None	None	N
I/M	0.314	likely_benign	0.288	benign	-1.385	Destabilizing	0.991	D	0.701	prob.neutral	N	0.487168862	None	None	N
I/N	0.7847	likely_pathogenic	0.7517	pathogenic	-2.768	Highly Destabilizing	0.997	D	0.787	deleterious	N	0.473113077	None	None	N
I/P	0.9982	likely_pathogenic	0.9976	pathogenic	-1.95	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
I/Q	0.9006	likely_pathogenic	0.8756	pathogenic	-2.671	Highly Destabilizing	0.998	D	0.776	deleterious	None	None	None	None	N
I/R	0.8492	likely_pathogenic	0.8214	pathogenic	-1.966	Destabilizing	0.993	D	0.783	deleterious	None	None	None	None	N
I/S	0.8447	likely_pathogenic	0.8102	pathogenic	-3.361	Highly Destabilizing	0.991	D	0.665	neutral	N	0.470199788	None	None	N
I/T	0.7463	likely_pathogenic	0.7034	pathogenic	-3.035	Highly Destabilizing	0.939	D	0.678	prob.neutral	N	0.500527759	None	None	N
I/V	0.1082	likely_benign	0.1058	benign	-1.95	Destabilizing	0.02	N	0.256	neutral	N	0.495564657	None	None	N
I/W	0.9514	likely_pathogenic	0.9321	pathogenic	-2.234	Highly Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
I/Y	0.7872	likely_pathogenic	0.7538	pathogenic	-2.016	Highly Destabilizing	0.993	D	0.709	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.