TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17197	51814;51815;51816	chr2:178609834;178609833;178609832	chr2:179474561;179474560;179474559
N2AB	15556	46891;46892;46893	chr2:178609834;178609833;178609832	chr2:179474561;179474560;179474559
N2A	14629	44110;44111;44112	chr2:178609834;178609833;178609832	chr2:179474561;179474560;179474559
N2B	8132	24619;24620;24621	chr2:178609834;178609833;178609832	chr2:179474561;179474560;179474559
Novex-1	8257	24994;24995;24996	chr2:178609834;178609833;178609832	chr2:179474561;179474560;179474559
Novex-2	8324	25195;25196;25197	chr2:178609834;178609833;178609832	chr2:179474561;179474560;179474559
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-13
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2306
• 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
C/Y	None	None	0.999	N	0.759	0.39	0.621043220472	gnomAD-4.0.0	1.36894E-06	None	None	None	None	I	None	0	0	None	0	2.52029E-05	None	0	0	8.99797E-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
C/A	0.7039	likely_pathogenic	0.6873	pathogenic	-1.842	Destabilizing	0.964	D	0.429	neutral	None	None	None	None	I
C/D	0.9899	likely_pathogenic	0.9878	pathogenic	-0.478	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	I
C/E	0.9894	likely_pathogenic	0.9869	pathogenic	-0.345	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	I
C/F	0.7342	likely_pathogenic	0.7394	pathogenic	-1.16	Destabilizing	0.997	D	0.748	deleterious	N	0.521671036	None	None	I
C/G	0.7417	likely_pathogenic	0.7171	pathogenic	-2.172	Highly Destabilizing	0.999	D	0.709	prob.delet.	N	0.475354803	None	None	I
C/H	0.9702	likely_pathogenic	0.9674	pathogenic	-2.13	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
C/I	0.6019	likely_pathogenic	0.5742	pathogenic	-0.981	Destabilizing	0.971	D	0.503	neutral	None	None	None	None	I
C/K	0.9955	likely_pathogenic	0.9942	pathogenic	-1.047	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	I
C/L	0.6939	likely_pathogenic	0.7045	pathogenic	-0.981	Destabilizing	0.931	D	0.517	neutral	None	None	None	None	I
C/M	0.8315	likely_pathogenic	0.8234	pathogenic	0.062	Stabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	I
C/N	0.9541	likely_pathogenic	0.9481	pathogenic	-1.176	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
C/P	0.9924	likely_pathogenic	0.9923	pathogenic	-1.243	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
C/Q	0.9754	likely_pathogenic	0.9703	pathogenic	-0.985	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	I
C/R	0.972	likely_pathogenic	0.966	pathogenic	-0.99	Destabilizing	0.999	D	0.779	deleterious	N	0.491520047	None	None	I
C/S	0.7538	likely_pathogenic	0.7445	pathogenic	-1.708	Destabilizing	0.99	D	0.605	neutral	N	0.513283626	None	None	I
C/T	0.7758	likely_pathogenic	0.7668	pathogenic	-1.382	Destabilizing	0.985	D	0.563	neutral	None	None	None	None	I
C/V	0.4524	ambiguous	0.4189	ambiguous	-1.243	Destabilizing	0.469	N	0.358	neutral	None	None	None	None	I
C/W	0.9389	likely_pathogenic	0.9405	pathogenic	-1.19	Destabilizing	1.0	D	0.74	deleterious	N	0.505829321	None	None	I
C/Y	0.8838	likely_pathogenic	0.8813	pathogenic	-1.173	Destabilizing	0.999	D	0.759	deleterious	N	0.520903031	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.