TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19217	57874;57875;57876	chr2:178595705;178595704;178595703	chr2:179460432;179460431;179460430
N2AB	17576	52951;52952;52953	chr2:178595705;178595704;178595703	chr2:179460432;179460431;179460430
N2A	16649	50170;50171;50172	chr2:178595705;178595704;178595703	chr2:179460432;179460431;179460430
N2B	10152	30679;30680;30681	chr2:178595705;178595704;178595703	chr2:179460432;179460431;179460430
Novex-1	10277	31054;31055;31056	chr2:178595705;178595704;178595703	chr2:179460432;179460431;179460430
Novex-2	10344	31255;31256;31257	chr2:178595705;178595704;178595703	chr2:179460432;179460431;179460430
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-27
• Domain position: 35
• Structural Position: 36
• Q(SASA): 0.3462
• 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
T/A	None	None	0.999	N	0.565	0.456	0.298403945805	gnomAD-4.0.0	1.37294E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.3546E-05	0
T/I	None	None	1.0	N	0.86	0.41	0.485562757867	gnomAD-4.0.0	1.60349E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8752E-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
T/A	0.1928	likely_benign	0.1983	benign	-0.72	Destabilizing	0.999	D	0.565	neutral	N	0.487172543	None	None	I
T/C	0.5884	likely_pathogenic	0.5914	pathogenic	-0.447	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
T/D	0.8016	likely_pathogenic	0.8011	pathogenic	-0.446	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
T/E	0.667	likely_pathogenic	0.6819	pathogenic	-0.493	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
T/F	0.553	ambiguous	0.5737	pathogenic	-1.048	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	I
T/G	0.412	ambiguous	0.428	ambiguous	-0.91	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	I
T/H	0.467	ambiguous	0.4849	ambiguous	-1.285	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
T/I	0.4151	ambiguous	0.4078	ambiguous	-0.32	Destabilizing	1.0	D	0.86	deleterious	N	0.504053641	None	None	I
T/K	0.4256	ambiguous	0.4794	ambiguous	-0.714	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	I
T/L	0.2041	likely_benign	0.1995	benign	-0.32	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	I
T/M	0.1656	likely_benign	0.1693	benign	0.127	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/N	0.2816	likely_benign	0.2746	benign	-0.591	Destabilizing	1.0	D	0.805	deleterious	N	0.482906582	None	None	I
T/P	0.8225	likely_pathogenic	0.8169	pathogenic	-0.424	Destabilizing	1.0	D	0.849	deleterious	N	0.50688664	None	None	I
T/Q	0.3878	ambiguous	0.4069	ambiguous	-0.888	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I
T/R	0.3756	ambiguous	0.4365	ambiguous	-0.374	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	I
T/S	0.1662	likely_benign	0.1759	benign	-0.802	Destabilizing	0.999	D	0.578	neutral	N	0.470959788	None	None	I
T/V	0.3088	likely_benign	0.299	benign	-0.424	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	I
T/W	0.8422	likely_pathogenic	0.8558	pathogenic	-0.974	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
T/Y	0.6106	likely_pathogenic	0.6317	pathogenic	-0.733	Destabilizing	1.0	D	0.864	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.