TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21814	65665;65666;65667	chr2:178583742;178583741;178583740	chr2:179448469;179448468;179448467
N2AB	20173	60742;60743;60744	chr2:178583742;178583741;178583740	chr2:179448469;179448468;179448467
N2A	19246	57961;57962;57963	chr2:178583742;178583741;178583740	chr2:179448469;179448468;179448467
N2B	12749	38470;38471;38472	chr2:178583742;178583741;178583740	chr2:179448469;179448468;179448467
Novex-1	12874	38845;38846;38847	chr2:178583742;178583741;178583740	chr2:179448469;179448468;179448467
Novex-2	12941	39046;39047;39048	chr2:178583742;178583741;178583740	chr2:179448469;179448468;179448467
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-46
• Domain position: 58
• Structural Position: 77
• Q(SASA): 0.0667
• 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/T	rs781750612	-2.738	0.978	N	0.653	0.336	0.596373027241	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.67E-05	None	0	None	0	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	0.8154	likely_pathogenic	0.7788	pathogenic	-2.642	Highly Destabilizing	0.983	D	0.597	neutral	None	None	None	None	N
I/C	0.7996	likely_pathogenic	0.8079	pathogenic	-1.595	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
I/D	0.9564	likely_pathogenic	0.9455	pathogenic	-3.158	Highly Destabilizing	0.999	D	0.835	deleterious	None	None	None	None	N
I/E	0.9327	likely_pathogenic	0.9181	pathogenic	-2.881	Highly Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
I/F	0.4021	ambiguous	0.374	ambiguous	-1.602	Destabilizing	0.997	D	0.627	neutral	N	0.505336146	None	None	N
I/G	0.9496	likely_pathogenic	0.9314	pathogenic	-3.189	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
I/H	0.8797	likely_pathogenic	0.8554	pathogenic	-2.846	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
I/K	0.8717	likely_pathogenic	0.8274	pathogenic	-1.911	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
I/L	0.2163	likely_benign	0.1964	benign	-1.016	Destabilizing	0.798	D	0.377	neutral	N	0.481784496	None	None	N
I/M	0.2303	likely_benign	0.2026	benign	-1.01	Destabilizing	0.997	D	0.633	neutral	N	0.475706743	None	None	N
I/N	0.6097	likely_pathogenic	0.5728	pathogenic	-2.432	Highly Destabilizing	0.999	D	0.85	deleterious	N	0.49305053	None	None	N
I/P	0.9213	likely_pathogenic	0.8923	pathogenic	-1.546	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
I/Q	0.8729	likely_pathogenic	0.837	pathogenic	-2.177	Highly Destabilizing	0.999	D	0.847	deleterious	None	None	None	None	N
I/R	0.8482	likely_pathogenic	0.8115	pathogenic	-1.817	Destabilizing	0.999	D	0.85	deleterious	None	None	None	None	N
I/S	0.7632	likely_pathogenic	0.72	pathogenic	-2.994	Highly Destabilizing	0.997	D	0.713	prob.delet.	N	0.500255613	None	None	N
I/T	0.7938	likely_pathogenic	0.7358	pathogenic	-2.579	Highly Destabilizing	0.978	D	0.653	neutral	N	0.497946027	None	None	N
I/V	0.1247	likely_benign	0.1119	benign	-1.546	Destabilizing	0.198	N	0.195	neutral	N	0.406460018	None	None	N
I/W	0.944	likely_pathogenic	0.9422	pathogenic	-2.066	Highly Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
I/Y	0.7895	likely_pathogenic	0.7772	pathogenic	-1.798	Destabilizing	0.999	D	0.729	prob.delet.	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.