TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25520	76783;76784;76785	chr2:178569574;178569573;178569572	chr2:179434301;179434300;179434299
N2AB	23879	71860;71861;71862	chr2:178569574;178569573;178569572	chr2:179434301;179434300;179434299
N2A	22952	69079;69080;69081	chr2:178569574;178569573;178569572	chr2:179434301;179434300;179434299
N2B	16455	49588;49589;49590	chr2:178569574;178569573;178569572	chr2:179434301;179434300;179434299
Novex-1	16580	49963;49964;49965	chr2:178569574;178569573;178569572	chr2:179434301;179434300;179434299
Novex-2	16647	50164;50165;50166	chr2:178569574;178569573;178569572	chr2:179434301;179434300;179434299
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-135
• Domain position: 7
• Structural Position: 13
• Q(SASA): 0.1457
• 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/T	rs1553601714	None	0.22	N	0.641	0.365	0.665058716224	gnomAD-4.0.0	1.36904E-06	None	None	None	None	I	None	0	0	None	0	2.53024E-05	None	0	0	8.99666E-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
I/A	0.6168	likely_pathogenic	0.6329	pathogenic	-2.035	Highly Destabilizing	0.072	N	0.618	neutral	None	None	None	None	I
I/C	0.6945	likely_pathogenic	0.715	pathogenic	-1.43	Destabilizing	0.968	D	0.651	neutral	None	None	None	None	I
I/D	0.9491	likely_pathogenic	0.9576	pathogenic	-1.456	Destabilizing	0.89	D	0.767	deleterious	None	None	None	None	I
I/E	0.8675	likely_pathogenic	0.8896	pathogenic	-1.355	Destabilizing	0.726	D	0.754	deleterious	None	None	None	None	I
I/F	0.2665	likely_benign	0.2701	benign	-1.254	Destabilizing	0.396	N	0.591	neutral	None	None	None	None	I
I/G	0.8874	likely_pathogenic	0.8945	pathogenic	-2.469	Highly Destabilizing	0.726	D	0.731	prob.delet.	None	None	None	None	I
I/H	0.7034	likely_pathogenic	0.722	pathogenic	-1.651	Destabilizing	0.968	D	0.747	deleterious	None	None	None	None	I
I/K	0.662	likely_pathogenic	0.7097	pathogenic	-1.522	Destabilizing	0.667	D	0.747	deleterious	N	0.493583276	None	None	I
I/L	0.1112	likely_benign	0.1164	benign	-0.862	Destabilizing	None	N	0.218	neutral	N	0.462562096	None	None	I
I/M	0.1176	likely_benign	0.1254	benign	-0.758	Destabilizing	0.331	N	0.6	neutral	D	0.527403008	None	None	I
I/N	0.5854	likely_pathogenic	0.6086	pathogenic	-1.531	Destabilizing	0.89	D	0.771	deleterious	None	None	None	None	I
I/P	0.9549	likely_pathogenic	0.9587	pathogenic	-1.224	Destabilizing	0.89	D	0.765	deleterious	None	None	None	None	I
I/Q	0.6506	likely_pathogenic	0.6847	pathogenic	-1.557	Destabilizing	0.89	D	0.762	deleterious	None	None	None	None	I
I/R	0.5989	likely_pathogenic	0.6401	pathogenic	-1.04	Destabilizing	0.667	D	0.77	deleterious	N	0.516802866	None	None	I
I/S	0.6216	likely_pathogenic	0.6353	pathogenic	-2.26	Highly Destabilizing	0.726	D	0.689	prob.neutral	None	None	None	None	I
I/T	0.43	ambiguous	0.4417	ambiguous	-2.016	Highly Destabilizing	0.22	N	0.641	neutral	N	0.486074858	None	None	I
I/V	0.0758	likely_benign	0.0766	benign	-1.224	Destabilizing	None	N	0.198	neutral	N	0.401529493	None	None	I
I/W	0.8513	likely_pathogenic	0.8647	pathogenic	-1.403	Destabilizing	0.968	D	0.733	prob.delet.	None	None	None	None	I
I/Y	0.6652	likely_pathogenic	0.6852	pathogenic	-1.166	Destabilizing	0.726	D	0.699	prob.neutral	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.