TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10047	30364;30365;30366	chr2:178704231;178704230;178704229	chr2:179568958;179568957;179568956
N2AB	9730	29413;29414;29415	chr2:178704231;178704230;178704229	chr2:179568958;179568957;179568956
N2A	8803	26632;26633;26634	chr2:178704231;178704230;178704229	chr2:179568958;179568957;179568956
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-85
• Domain position: 59
• Structural Position: 140
• Q(SASA): 0.0757
• 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	rs1468010768	None	1.0	None	0.827	0.804	0.865251336291	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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	0.9566	likely_pathogenic	0.9787	pathogenic	-2.775	Highly Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
I/C	0.991	likely_pathogenic	0.9965	pathogenic	-2.42	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
I/D	0.9988	likely_pathogenic	0.9991	pathogenic	-3.615	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
I/E	0.9969	likely_pathogenic	0.9974	pathogenic	-3.451	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
I/F	0.6463	likely_pathogenic	0.7405	pathogenic	-1.754	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/G	0.9975	likely_pathogenic	0.9986	pathogenic	-3.265	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/H	0.9945	likely_pathogenic	0.9966	pathogenic	-2.636	Highly Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
I/K	0.9916	likely_pathogenic	0.9933	pathogenic	-2.315	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
I/L	0.353	ambiguous	0.4336	ambiguous	-1.367	Destabilizing	0.993	D	0.413	neutral	None	None	None	None	N
I/M	0.3625	ambiguous	0.4547	ambiguous	-1.342	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
I/N	0.9883	likely_pathogenic	0.9911	pathogenic	-2.643	Highly Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
I/P	0.9983	likely_pathogenic	0.999	pathogenic	-1.818	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
I/Q	0.9941	likely_pathogenic	0.9957	pathogenic	-2.61	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
I/R	0.9865	likely_pathogenic	0.9897	pathogenic	-1.813	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
I/S	0.9805	likely_pathogenic	0.9878	pathogenic	-3.243	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
I/T	0.9484	likely_pathogenic	0.9741	pathogenic	-2.95	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
I/V	0.1496	likely_benign	0.2342	benign	-1.818	Destabilizing	0.993	D	0.395	neutral	None	None	None	None	N
I/W	0.9905	likely_pathogenic	0.9944	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
I/Y	0.9716	likely_pathogenic	0.9831	pathogenic	-1.97	Destabilizing	1.0	D	0.848	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.