TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16482	49669;49670;49671	chr2:178613839;178613838;178613837	chr2:179478566;179478565;179478564
N2AB	14841	44746;44747;44748	chr2:178613839;178613838;178613837	chr2:179478566;179478565;179478564
N2A	13914	41965;41966;41967	chr2:178613839;178613838;178613837	chr2:179478566;179478565;179478564
N2B	7417	22474;22475;22476	chr2:178613839;178613838;178613837	chr2:179478566;179478565;179478564
Novex-1	7542	22849;22850;22851	chr2:178613839;178613838;178613837	chr2:179478566;179478565;179478564
Novex-2	7609	23050;23051;23052	chr2:178613839;178613838;178613837	chr2:179478566;179478565;179478564
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: Fn3-7
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1913
• 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
I/V	rs1029563364	None	0.993	N	0.387	0.264	0.524792858863	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs1029563364	None	0.993	N	0.387	0.264	0.524792858863	gnomAD-4.0.0	5.58158E-06	None	None	None	None	I	None	0	1.66917E-05	None	0	0	None	0	0	6.7849E-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	0.9713	likely_pathogenic	0.9649	pathogenic	-2.323	Highly Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
I/C	0.9796	likely_pathogenic	0.9731	pathogenic	-1.434	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
I/D	0.999	likely_pathogenic	0.9989	pathogenic	-2.251	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
I/E	0.9958	likely_pathogenic	0.9952	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
I/F	0.948	likely_pathogenic	0.9428	pathogenic	-1.627	Destabilizing	1.0	D	0.829	deleterious	D	0.713320152	None	None	I
I/G	0.9971	likely_pathogenic	0.9966	pathogenic	-2.742	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
I/H	0.9972	likely_pathogenic	0.9966	pathogenic	-2.043	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
I/K	0.991	likely_pathogenic	0.9898	pathogenic	-1.691	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
I/L	0.522	ambiguous	0.4529	ambiguous	-1.179	Destabilizing	0.993	D	0.406	neutral	D	0.529509263	None	None	I
I/M	0.6913	likely_pathogenic	0.6597	pathogenic	-0.844	Destabilizing	1.0	D	0.805	deleterious	D	0.717483038	None	None	I
I/N	0.9789	likely_pathogenic	0.9748	pathogenic	-1.643	Destabilizing	1.0	D	0.872	deleterious	D	0.703371777	None	None	I
I/P	0.9755	likely_pathogenic	0.97	pathogenic	-1.535	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
I/Q	0.9949	likely_pathogenic	0.9936	pathogenic	-1.753	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
I/R	0.9889	likely_pathogenic	0.9876	pathogenic	-1.109	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
I/S	0.9842	likely_pathogenic	0.9813	pathogenic	-2.289	Highly Destabilizing	1.0	D	0.867	deleterious	D	0.738615732	None	None	I
I/T	0.9494	likely_pathogenic	0.9438	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.843	deleterious	D	0.657265295	None	None	I
I/V	0.0742	likely_benign	0.0766	benign	-1.535	Destabilizing	0.993	D	0.387	neutral	N	0.479806484	None	None	I
I/W	0.9989	likely_pathogenic	0.9989	pathogenic	-1.848	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
I/Y	0.994	likely_pathogenic	0.9935	pathogenic	-1.621	Destabilizing	1.0	D	0.862	deleterious	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.