TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26120	78583;78584;78585	chr2:178567774;178567773;178567772	chr2:179432501;179432500;179432499
N2AB	24479	73660;73661;73662	chr2:178567774;178567773;178567772	chr2:179432501;179432500;179432499
N2A	23552	70879;70880;70881	chr2:178567774;178567773;178567772	chr2:179432501;179432500;179432499
N2B	17055	51388;51389;51390	chr2:178567774;178567773;178567772	chr2:179432501;179432500;179432499
Novex-1	17180	51763;51764;51765	chr2:178567774;178567773;178567772	chr2:179432501;179432500;179432499
Novex-2	17247	51964;51965;51966	chr2:178567774;178567773;178567772	chr2:179432501;179432500;179432499
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: Fn3-78
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1393
• 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/F	None	None	0.994	D	0.669	0.427	0.684186827415	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.9732	likely_pathogenic	0.9674	pathogenic	-2.21	Highly Destabilizing	0.931	D	0.677	prob.neutral	None	None	None	None	I
I/C	0.9803	likely_pathogenic	0.973	pathogenic	-1.42	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	I
I/D	0.9982	likely_pathogenic	0.9978	pathogenic	-2.304	Highly Destabilizing	0.999	D	0.852	deleterious	None	None	None	None	I
I/E	0.9938	likely_pathogenic	0.9928	pathogenic	-2.248	Highly Destabilizing	0.999	D	0.842	deleterious	None	None	None	None	I
I/F	0.9137	likely_pathogenic	0.8986	pathogenic	-1.644	Destabilizing	0.994	D	0.669	neutral	D	0.533424366	None	None	I
I/G	0.9955	likely_pathogenic	0.9943	pathogenic	-2.606	Highly Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	I
I/H	0.9947	likely_pathogenic	0.9927	pathogenic	-1.946	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
I/K	0.9856	likely_pathogenic	0.9838	pathogenic	-1.569	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	I
I/L	0.3897	ambiguous	0.3511	ambiguous	-1.141	Destabilizing	0.689	D	0.469	neutral	N	0.508846172	None	None	I
I/M	0.5685	likely_pathogenic	0.5149	ambiguous	-0.798	Destabilizing	0.994	D	0.652	neutral	D	0.535959261	None	None	I
I/N	0.9342	likely_pathogenic	0.9196	pathogenic	-1.518	Destabilizing	0.998	D	0.861	deleterious	D	0.523148152	None	None	I
I/P	0.9717	likely_pathogenic	0.9686	pathogenic	-1.471	Destabilizing	0.999	D	0.858	deleterious	None	None	None	None	I
I/Q	0.9903	likely_pathogenic	0.9883	pathogenic	-1.665	Destabilizing	0.999	D	0.865	deleterious	None	None	None	None	I
I/R	0.9824	likely_pathogenic	0.9796	pathogenic	-0.978	Destabilizing	0.999	D	0.864	deleterious	None	None	None	None	I
I/S	0.9784	likely_pathogenic	0.9755	pathogenic	-2.126	Highly Destabilizing	0.994	D	0.831	deleterious	D	0.524856445	None	None	I
I/T	0.9483	likely_pathogenic	0.9386	pathogenic	-1.95	Destabilizing	0.961	D	0.753	deleterious	N	0.520083505	None	None	I
I/V	0.1108	likely_benign	0.1059	benign	-1.471	Destabilizing	0.122	N	0.253	neutral	N	0.4705385	None	None	I
I/W	0.9982	likely_pathogenic	0.9971	pathogenic	-1.864	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
I/Y	0.9873	likely_pathogenic	0.9844	pathogenic	-1.628	Destabilizing	0.999	D	0.811	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.