TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6309	19150;19151;19152	chr2:178729113;178729112;178729111	chr2:179593840;179593839;179593838
N2AB	5992	18199;18200;18201	chr2:178729113;178729112;178729111	chr2:179593840;179593839;179593838
N2A	5065	15418;15419;15420	chr2:178729113;178729112;178729111	chr2:179593840;179593839;179593838
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-47
• Domain position: 18
• Structural Position: 28
• Q(SASA): 0.2326
• 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
A/S	None	None	0.201	N	0.643	0.326	0.148003135375	gnomAD-4.0.0	1.60346E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87523E-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
A/C	0.6144	likely_pathogenic	0.5806	pathogenic	-1.078	Destabilizing	0.982	D	0.673	neutral	None	None	None	None	I
A/D	0.9261	likely_pathogenic	0.9002	pathogenic	-0.469	Destabilizing	0.638	D	0.809	deleterious	N	0.509376677	None	None	I
A/E	0.8613	likely_pathogenic	0.8294	pathogenic	-0.461	Destabilizing	0.826	D	0.807	deleterious	None	None	None	None	I
A/F	0.709	likely_pathogenic	0.6686	pathogenic	-0.855	Destabilizing	0.826	D	0.805	deleterious	None	None	None	None	I
A/G	0.3475	ambiguous	0.3362	benign	-1.108	Destabilizing	0.002	N	0.369	neutral	N	0.485992503	None	None	I
A/H	0.9201	likely_pathogenic	0.8997	pathogenic	-1.18	Destabilizing	0.982	D	0.765	deleterious	None	None	None	None	I
A/I	0.2727	likely_benign	0.2385	benign	-0.14	Destabilizing	0.25	N	0.769	deleterious	None	None	None	None	I
A/K	0.9233	likely_pathogenic	0.9037	pathogenic	-0.866	Destabilizing	0.7	D	0.807	deleterious	None	None	None	None	I
A/L	0.3606	ambiguous	0.3275	benign	-0.14	Destabilizing	0.25	N	0.667	neutral	None	None	None	None	I
A/M	0.4186	ambiguous	0.3747	ambiguous	-0.318	Destabilizing	0.947	D	0.76	deleterious	None	None	None	None	I
A/N	0.8381	likely_pathogenic	0.7985	pathogenic	-0.689	Destabilizing	0.7	D	0.81	deleterious	None	None	None	None	I
A/P	0.9147	likely_pathogenic	0.9026	pathogenic	-0.32	Destabilizing	0.781	D	0.815	deleterious	N	0.486245992	None	None	I
A/Q	0.8393	likely_pathogenic	0.8059	pathogenic	-0.747	Destabilizing	0.826	D	0.799	deleterious	None	None	None	None	I
A/R	0.8807	likely_pathogenic	0.8585	pathogenic	-0.693	Destabilizing	0.826	D	0.811	deleterious	None	None	None	None	I
A/S	0.2072	likely_benign	0.194	benign	-1.212	Destabilizing	0.201	N	0.643	neutral	N	0.482371652	None	None	I
A/T	0.1219	likely_benign	0.1135	benign	-1.075	Destabilizing	0.334	N	0.677	prob.neutral	N	0.494806934	None	None	I
A/V	0.1089	likely_benign	0.0985	benign	-0.32	Destabilizing	0.007	N	0.291	neutral	N	0.38349744	None	None	I
A/W	0.9744	likely_pathogenic	0.9664	pathogenic	-1.172	Destabilizing	0.982	D	0.736	prob.delet.	None	None	None	None	I
A/Y	0.8944	likely_pathogenic	0.875	pathogenic	-0.727	Destabilizing	0.935	D	0.815	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.