TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16341	49246;49247;49248	chr2:178614493;178614492;178614491	chr2:179479220;179479219;179479218
N2AB	14700	44323;44324;44325	chr2:178614493;178614492;178614491	chr2:179479220;179479219;179479218
N2A	13773	41542;41543;41544	chr2:178614493;178614492;178614491	chr2:179479220;179479219;179479218
N2B	7276	22051;22052;22053	chr2:178614493;178614492;178614491	chr2:179479220;179479219;179479218
Novex-1	7401	22426;22427;22428	chr2:178614493;178614492;178614491	chr2:179479220;179479219;179479218
Novex-2	7468	22627;22628;22629	chr2:178614493;178614492;178614491	chr2:179479220;179479219;179479218
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-110
• Domain position: 80
• Structural Position: 168
• Q(SASA): 0.5783
• 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/S	None	None	0.999	N	0.519	0.322	0.410734915765	gnomAD-4.0.0	1.60165E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87684E-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	0.2851	likely_benign	0.3838	ambiguous	-0.261	Destabilizing	0.999	D	0.524	neutral	D	0.581465085	None	None	I
T/C	0.8619	likely_pathogenic	0.9055	pathogenic	-0.339	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
T/D	0.9176	likely_pathogenic	0.9541	pathogenic	0.149	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
T/E	0.8358	likely_pathogenic	0.9031	pathogenic	0.09	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
T/F	0.8123	likely_pathogenic	0.8899	pathogenic	-0.674	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	I
T/G	0.7625	likely_pathogenic	0.8245	pathogenic	-0.413	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
T/H	0.7616	likely_pathogenic	0.8579	pathogenic	-0.655	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
T/I	0.6922	likely_pathogenic	0.8108	pathogenic	0.02	Stabilizing	1.0	D	0.855	deleterious	D	0.549507558	None	None	I
T/K	0.6732	likely_pathogenic	0.7887	pathogenic	-0.417	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
T/L	0.4845	ambiguous	0.6	pathogenic	0.02	Stabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
T/M	0.252	likely_benign	0.39	ambiguous	-0.024	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
T/N	0.5388	ambiguous	0.6726	pathogenic	-0.233	Destabilizing	1.0	D	0.749	deleterious	N	0.517704472	None	None	I
T/P	0.8639	likely_pathogenic	0.875	pathogenic	-0.044	Destabilizing	1.0	D	0.848	deleterious	D	0.671119165	None	None	I
T/Q	0.6521	likely_pathogenic	0.7722	pathogenic	-0.405	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	I
T/R	0.669	likely_pathogenic	0.7907	pathogenic	-0.157	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
T/S	0.3141	likely_benign	0.4313	ambiguous	-0.42	Destabilizing	0.999	D	0.519	neutral	N	0.479635431	None	None	I
T/V	0.443	ambiguous	0.5492	ambiguous	-0.044	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	I
T/W	0.9517	likely_pathogenic	0.9744	pathogenic	-0.719	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
T/Y	0.8441	likely_pathogenic	0.9049	pathogenic	-0.425	Destabilizing	1.0	D	0.859	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.