TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2161	6706;6707;6708	chr2:178775383;178775382;178775381	chr2:179640110;179640109;179640108
N2AB	2161	6706;6707;6708	chr2:178775383;178775382;178775381	chr2:179640110;179640109;179640108
N2A	2161	6706;6707;6708	chr2:178775383;178775382;178775381	chr2:179640110;179640109;179640108
N2B	2115	6568;6569;6570	chr2:178775383;178775382;178775381	chr2:179640110;179640109;179640108
Novex-1	2115	6568;6569;6570	chr2:178775383;178775382;178775381	chr2:179640110;179640109;179640108
Novex-2	2115	6568;6569;6570	chr2:178775383;178775382;178775381	chr2:179640110;179640109;179640108
Novex-3	2161	6706;6707;6708	chr2:178775383;178775382;178775381	chr2:179640110;179640109;179640108

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-10
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.2297
• 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
S/T	None	None	0.999	N	0.483	0.332	0.394230963961	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
S/A	0.1639	likely_benign	0.1718	benign	-0.461	Destabilizing	0.997	D	0.45	neutral	D	0.63504657	None	None	I
S/C	0.4078	ambiguous	0.4246	ambiguous	-0.371	Destabilizing	1.0	D	0.839	deleterious	D	0.648974604	None	None	I
S/D	0.9315	likely_pathogenic	0.9562	pathogenic	0.038	Stabilizing	0.999	D	0.58	neutral	None	None	None	None	I
S/E	0.9361	likely_pathogenic	0.9544	pathogenic	0.015	Stabilizing	0.999	D	0.55	neutral	None	None	None	None	I
S/F	0.6849	likely_pathogenic	0.7691	pathogenic	-0.678	Destabilizing	1.0	D	0.907	deleterious	D	0.587901607	None	None	I
S/G	0.3143	likely_benign	0.3426	ambiguous	-0.688	Destabilizing	0.999	D	0.525	neutral	None	None	None	None	I
S/H	0.7904	likely_pathogenic	0.8542	pathogenic	-1.163	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
S/I	0.6453	likely_pathogenic	0.7091	pathogenic	0.025	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
S/K	0.982	likely_pathogenic	0.9865	pathogenic	-0.655	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	I
S/L	0.4556	ambiguous	0.5298	ambiguous	0.025	Stabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
S/M	0.5842	likely_pathogenic	0.6318	pathogenic	0.122	Stabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
S/N	0.5464	ambiguous	0.6308	pathogenic	-0.509	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	I
S/P	0.9801	likely_pathogenic	0.9852	pathogenic	-0.103	Destabilizing	1.0	D	0.867	deleterious	D	0.699150584	None	None	I
S/Q	0.8767	likely_pathogenic	0.9053	pathogenic	-0.633	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
S/R	0.9578	likely_pathogenic	0.971	pathogenic	-0.55	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	I
S/T	0.2053	likely_benign	0.2297	benign	-0.527	Destabilizing	0.999	D	0.483	neutral	N	0.503373636	None	None	I
S/V	0.5524	ambiguous	0.6253	pathogenic	-0.103	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	I
S/W	0.8481	likely_pathogenic	0.9026	pathogenic	-0.7	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	I
S/Y	0.6485	likely_pathogenic	0.746	pathogenic	-0.425	Destabilizing	1.0	D	0.909	deleterious	D	0.597122429	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.