TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21965	66118;66119;66120	chr2:178582563;178582562;178582561	chr2:179447290;179447289;179447288
N2AB	20324	61195;61196;61197	chr2:178582563;178582562;178582561	chr2:179447290;179447289;179447288
N2A	19397	58414;58415;58416	chr2:178582563;178582562;178582561	chr2:179447290;179447289;179447288
N2B	12900	38923;38924;38925	chr2:178582563;178582562;178582561	chr2:179447290;179447289;179447288
Novex-1	13025	39298;39299;39300	chr2:178582563;178582562;178582561	chr2:179447290;179447289;179447288
Novex-2	13092	39499;39500;39501	chr2:178582563;178582562;178582561	chr2:179447290;179447289;179447288
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: Fn3-47
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3019
• 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/M	None	None	0.999	N	0.572	0.367	0.470072546239	gnomAD-4.0.0	3.19797E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.77031E-05	0	0	0	0
I/T	rs1575938216	None	0.4	N	0.377	0.23	0.526943034955	gnomAD-4.0.0	2.05676E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	4.98041E-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
I/A	0.8948	likely_pathogenic	0.8535	pathogenic	-1.906	Destabilizing	0.469	N	0.327	neutral	None	None	None	None	N
I/C	0.888	likely_pathogenic	0.8502	pathogenic	-1.131	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
I/D	0.9846	likely_pathogenic	0.9763	pathogenic	-1.363	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
I/E	0.9568	likely_pathogenic	0.9337	pathogenic	-1.327	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
I/F	0.3894	ambiguous	0.3546	ambiguous	-1.332	Destabilizing	0.999	D	0.605	neutral	N	0.507416446	None	None	N
I/G	0.9721	likely_pathogenic	0.9562	pathogenic	-2.283	Highly Destabilizing	0.985	D	0.747	deleterious	None	None	None	None	N
I/H	0.9492	likely_pathogenic	0.9239	pathogenic	-1.541	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
I/K	0.8971	likely_pathogenic	0.8373	pathogenic	-1.313	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
I/L	0.2438	likely_benign	0.1988	benign	-0.918	Destabilizing	0.953	D	0.445	neutral	N	0.487734607	None	None	N
I/M	0.1919	likely_benign	0.1609	benign	-0.677	Destabilizing	0.999	D	0.572	neutral	N	0.495869049	None	None	N
I/N	0.8507	likely_pathogenic	0.7927	pathogenic	-1.12	Destabilizing	0.997	D	0.798	deleterious	N	0.507985823	None	None	N
I/P	0.9212	likely_pathogenic	0.8812	pathogenic	-1.217	Destabilizing	0.999	D	0.799	deleterious	None	None	None	None	N
I/Q	0.9185	likely_pathogenic	0.8782	pathogenic	-1.253	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	N
I/R	0.8841	likely_pathogenic	0.8225	pathogenic	-0.765	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
I/S	0.911	likely_pathogenic	0.8752	pathogenic	-1.773	Destabilizing	0.961	D	0.661	neutral	N	0.489121099	None	None	N
I/T	0.8621	likely_pathogenic	0.8159	pathogenic	-1.608	Destabilizing	0.4	N	0.377	neutral	N	0.478018283	None	None	N
I/V	0.1495	likely_benign	0.1381	benign	-1.217	Destabilizing	0.899	D	0.442	neutral	N	0.418986598	None	None	N
I/W	0.8916	likely_pathogenic	0.8669	pathogenic	-1.44	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
I/Y	0.8094	likely_pathogenic	0.7585	pathogenic	-1.222	Destabilizing	0.999	D	0.691	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.