TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24155	72688;72689;72690	chr2:178573669;178573668;178573667	chr2:179438396;179438395;179438394
N2AB	22514	67765;67766;67767	chr2:178573669;178573668;178573667	chr2:179438396;179438395;179438394
N2A	21587	64984;64985;64986	chr2:178573669;178573668;178573667	chr2:179438396;179438395;179438394
N2B	15090	45493;45494;45495	chr2:178573669;178573668;178573667	chr2:179438396;179438395;179438394
Novex-1	15215	45868;45869;45870	chr2:178573669;178573668;178573667	chr2:179438396;179438395;179438394
Novex-2	15282	46069;46070;46071	chr2:178573669;178573668;178573667	chr2:179438396;179438395;179438394
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: Fn3-63
• Domain position: 34
• Structural Position: 35
• Q(SASA): 0.1765
• 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	rs946539839	None	1.0	D	0.84	0.556	0.765966819243	gnomAD-4.0.0	2.93253E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.75184E-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	0.81	likely_pathogenic	0.8174	pathogenic	-2.4	Highly Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
I/C	0.9438	likely_pathogenic	0.9486	pathogenic	-1.391	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
I/D	0.9963	likely_pathogenic	0.9955	pathogenic	-2.463	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
I/E	0.9868	likely_pathogenic	0.9842	pathogenic	-2.389	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	I
I/F	0.8653	likely_pathogenic	0.8486	pathogenic	-1.651	Destabilizing	1.0	D	0.837	deleterious	D	0.540172316	None	None	I
I/G	0.9831	likely_pathogenic	0.9831	pathogenic	-2.812	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
I/H	0.9927	likely_pathogenic	0.9915	pathogenic	-2.15	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
I/K	0.9798	likely_pathogenic	0.9752	pathogenic	-1.833	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
I/L	0.3213	likely_benign	0.3293	benign	-1.267	Destabilizing	0.993	D	0.431	neutral	N	0.491771353	None	None	I
I/M	0.3115	likely_benign	0.3253	benign	-0.858	Destabilizing	1.0	D	0.817	deleterious	D	0.549290576	None	None	I
I/N	0.9413	likely_pathogenic	0.9364	pathogenic	-1.745	Destabilizing	1.0	D	0.879	deleterious	D	0.543721169	None	None	I
I/P	0.9334	likely_pathogenic	0.9357	pathogenic	-1.62	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	I
I/Q	0.9838	likely_pathogenic	0.9816	pathogenic	-1.861	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	I
I/R	0.9709	likely_pathogenic	0.9668	pathogenic	-1.224	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	I
I/S	0.918	likely_pathogenic	0.9177	pathogenic	-2.341	Highly Destabilizing	1.0	D	0.872	deleterious	D	0.53818776	None	None	I
I/T	0.5572	ambiguous	0.5729	pathogenic	-2.152	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.528971049	None	None	I
I/V	0.0994	likely_benign	0.0996	benign	-1.62	Destabilizing	0.993	D	0.407	neutral	N	0.503938998	None	None	I
I/W	0.994	likely_pathogenic	0.9923	pathogenic	-1.898	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
I/Y	0.9787	likely_pathogenic	0.976	pathogenic	-1.698	Destabilizing	1.0	D	0.862	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.