TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13692	41299;41300;41301	chr2:178636653;178636652;178636651	chr2:179501380;179501379;179501378
N2AB	12051	36376;36377;36378	chr2:178636653;178636652;178636651	chr2:179501380;179501379;179501378
N2A	11124	33595;33596;33597	chr2:178636653;178636652;178636651	chr2:179501380;179501379;179501378
N2B	4627	14104;14105;14106	chr2:178636653;178636652;178636651	chr2:179501380;179501379;179501378
Novex-1	4752	14479;14480;14481	chr2:178636653;178636652;178636651	chr2:179501380;179501379;179501378
Novex-2	4819	14680;14681;14682	chr2:178636653;178636652;178636651	chr2:179501380;179501379;179501378
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: Ig-87
• Domain position: 9
• Structural Position: 13
• Q(SASA): 0.0656
• 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	None	None	1.0	D	0.72	0.622	0.810854131144	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.9605	likely_pathogenic	0.9122	pathogenic	-1.744	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
I/C	0.9814	likely_pathogenic	0.9615	pathogenic	-0.998	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
I/D	0.9952	likely_pathogenic	0.9888	pathogenic	-1.553	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
I/E	0.9821	likely_pathogenic	0.9553	pathogenic	-1.419	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/F	0.811	likely_pathogenic	0.6933	pathogenic	-0.986	Destabilizing	1.0	D	0.698	prob.neutral	D	0.592483123	None	None	N
I/G	0.9953	likely_pathogenic	0.9887	pathogenic	-2.186	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
I/H	0.9822	likely_pathogenic	0.9485	pathogenic	-1.492	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
I/K	0.949	likely_pathogenic	0.8828	pathogenic	-1.28	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
I/L	0.534	ambiguous	0.3715	ambiguous	-0.538	Destabilizing	0.993	D	0.339	neutral	N	0.486000437	None	None	N
I/M	0.4245	ambiguous	0.2704	benign	-0.435	Destabilizing	1.0	D	0.704	prob.neutral	D	0.54523123	None	None	N
I/N	0.9436	likely_pathogenic	0.8678	pathogenic	-1.409	Destabilizing	1.0	D	0.849	deleterious	D	0.685126785	None	None	N
I/P	0.9984	likely_pathogenic	0.9977	pathogenic	-0.913	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
I/Q	0.965	likely_pathogenic	0.8797	pathogenic	-1.386	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
I/R	0.9283	likely_pathogenic	0.8474	pathogenic	-0.907	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
I/S	0.9652	likely_pathogenic	0.9151	pathogenic	-2.05	Highly Destabilizing	1.0	D	0.763	deleterious	D	0.549600559	None	None	N
I/T	0.8882	likely_pathogenic	0.7587	pathogenic	-1.783	Destabilizing	1.0	D	0.72	prob.delet.	D	0.528836111	None	None	N
I/V	0.2476	likely_benign	0.1728	benign	-0.913	Destabilizing	0.993	D	0.303	neutral	N	0.478192675	None	None	N
I/W	0.9923	likely_pathogenic	0.9862	pathogenic	-1.271	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
I/Y	0.96	likely_pathogenic	0.9358	pathogenic	-0.94	Destabilizing	1.0	D	0.783	deleterious	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.