TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24020	72283;72284;72285	chr2:178574074;178574073;178574072	chr2:179438801;179438800;179438799
N2AB	22379	67360;67361;67362	chr2:178574074;178574073;178574072	chr2:179438801;179438800;179438799
N2A	21452	64579;64580;64581	chr2:178574074;178574073;178574072	chr2:179438801;179438800;179438799
N2B	14955	45088;45089;45090	chr2:178574074;178574073;178574072	chr2:179438801;179438800;179438799
Novex-1	15080	45463;45464;45465	chr2:178574074;178574073;178574072	chr2:179438801;179438800;179438799
Novex-2	15147	45664;45665;45666	chr2:178574074;178574073;178574072	chr2:179438801;179438800;179438799
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-62
• Domain position: 97
• Structural Position: 130
• Q(SASA): 0.0668
• 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
C/F	None	None	0.966	N	0.708	0.467	0.688144402267	gnomAD-4.0.0	4.10624E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.398E-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
C/A	0.726	likely_pathogenic	0.7122	pathogenic	-0.957	Destabilizing	0.016	N	0.334	neutral	None	None	None	None	N
C/D	0.9991	likely_pathogenic	0.999	pathogenic	-1.848	Destabilizing	0.974	D	0.815	deleterious	None	None	None	None	N
C/E	0.9993	likely_pathogenic	0.9993	pathogenic	-1.685	Destabilizing	0.949	D	0.808	deleterious	None	None	None	None	N
C/F	0.9115	likely_pathogenic	0.9129	pathogenic	-0.891	Destabilizing	0.966	D	0.708	prob.delet.	N	0.477716254	None	None	N
C/G	0.8076	likely_pathogenic	0.8045	pathogenic	-1.198	Destabilizing	0.666	D	0.752	deleterious	N	0.477209275	None	None	N
C/H	0.9966	likely_pathogenic	0.9965	pathogenic	-1.804	Destabilizing	0.998	D	0.785	deleterious	None	None	None	None	N
C/I	0.7939	likely_pathogenic	0.7877	pathogenic	-0.356	Destabilizing	0.949	D	0.671	prob.neutral	None	None	None	None	N
C/K	0.9993	likely_pathogenic	0.9993	pathogenic	-0.848	Destabilizing	0.949	D	0.785	deleterious	None	None	None	None	N
C/L	0.7978	likely_pathogenic	0.7968	pathogenic	-0.356	Destabilizing	0.841	D	0.555	neutral	None	None	None	None	N
C/M	0.9383	likely_pathogenic	0.937	pathogenic	-0.123	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
C/N	0.9914	likely_pathogenic	0.9897	pathogenic	-1.307	Destabilizing	0.974	D	0.8	deleterious	None	None	None	None	N
C/P	0.9578	likely_pathogenic	0.939	pathogenic	-0.533	Destabilizing	0.974	D	0.801	deleterious	None	None	None	None	N
C/Q	0.9966	likely_pathogenic	0.9965	pathogenic	-1.043	Destabilizing	0.974	D	0.794	deleterious	None	None	None	None	N
C/R	0.9905	likely_pathogenic	0.9907	pathogenic	-1.211	Destabilizing	0.966	D	0.793	deleterious	N	0.46585297	None	None	N
C/S	0.866	likely_pathogenic	0.8665	pathogenic	-1.384	Destabilizing	0.666	D	0.593	neutral	N	0.476955785	None	None	N
C/T	0.9049	likely_pathogenic	0.8873	pathogenic	-1.089	Destabilizing	0.841	D	0.635	neutral	None	None	None	None	N
C/V	0.6313	likely_pathogenic	0.613	pathogenic	-0.533	Destabilizing	0.725	D	0.592	neutral	None	None	None	None	N
C/W	0.9922	likely_pathogenic	0.9934	pathogenic	-1.462	Destabilizing	0.997	D	0.71	prob.delet.	N	0.478476723	None	None	N
C/Y	0.9836	likely_pathogenic	0.9851	pathogenic	-1.051	Destabilizing	0.989	D	0.708	prob.delet.	N	0.466359949	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.