TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8230	24913;24914;24915	chr2:178718418;178718417;178718416	chr2:179583145;179583144;179583143
N2AB	7913	23962;23963;23964	chr2:178718418;178718417;178718416	chr2:179583145;179583144;179583143
N2A	6986	21181;21182;21183	chr2:178718418;178718417;178718416	chr2:179583145;179583144;179583143
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-67
• Domain position: 60
• Structural Position: 140
• Q(SASA): 0.1176
• 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/V	None	None	0.002	D	0.291	0.383	0.631027719221	gnomAD-4.0.0	1.5913E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88253E-05	0	0	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	0.9114	likely_pathogenic	0.9048	pathogenic	-2.485	Highly Destabilizing	0.176	N	0.547	neutral	None	None	None	None	N
I/C	0.902	likely_pathogenic	0.89	pathogenic	-1.854	Destabilizing	0.981	D	0.733	prob.delet.	None	None	None	None	N
I/D	0.9753	likely_pathogenic	0.9746	pathogenic	-2.491	Highly Destabilizing	0.704	D	0.755	deleterious	None	None	None	None	N
I/E	0.9593	likely_pathogenic	0.9604	pathogenic	-2.347	Highly Destabilizing	0.704	D	0.739	prob.delet.	None	None	None	None	N
I/F	0.3216	likely_benign	0.3106	benign	-1.482	Destabilizing	0.863	D	0.661	neutral	D	0.595008985	None	None	N
I/G	0.9697	likely_pathogenic	0.9709	pathogenic	-2.968	Highly Destabilizing	0.003	N	0.567	neutral	None	None	None	None	N
I/H	0.8975	likely_pathogenic	0.8917	pathogenic	-2.254	Highly Destabilizing	0.995	D	0.813	deleterious	None	None	None	None	N
I/K	0.8825	likely_pathogenic	0.8863	pathogenic	-1.939	Destabilizing	0.704	D	0.737	prob.delet.	None	None	None	None	N
I/L	0.2335	likely_benign	0.2214	benign	-1.127	Destabilizing	0.139	N	0.373	neutral	D	0.574930656	None	None	N
I/M	0.2195	likely_benign	0.2115	benign	-1.042	Destabilizing	0.139	N	0.386	neutral	D	0.620143488	None	None	N
I/N	0.7298	likely_pathogenic	0.7308	pathogenic	-2.035	Highly Destabilizing	0.642	D	0.767	deleterious	D	0.637575479	None	None	N
I/P	0.9929	likely_pathogenic	0.9936	pathogenic	-1.556	Destabilizing	0.944	D	0.797	deleterious	None	None	None	None	N
I/Q	0.9124	likely_pathogenic	0.9117	pathogenic	-2.036	Highly Destabilizing	0.944	D	0.801	deleterious	None	None	None	None	N
I/R	0.8505	likely_pathogenic	0.8583	pathogenic	-1.467	Destabilizing	0.944	D	0.793	deleterious	None	None	None	None	N
I/S	0.864	likely_pathogenic	0.8578	pathogenic	-2.753	Highly Destabilizing	0.065	N	0.555	neutral	D	0.637575479	None	None	N
I/T	0.8869	likely_pathogenic	0.8745	pathogenic	-2.476	Highly Destabilizing	0.023	N	0.5	neutral	D	0.621152509	None	None	N
I/V	0.1589	likely_benign	0.1378	benign	-1.556	Destabilizing	0.002	N	0.291	neutral	D	0.545720434	None	None	N
I/W	0.9451	likely_pathogenic	0.9357	pathogenic	-1.745	Destabilizing	0.995	D	0.802	deleterious	None	None	None	None	N
I/Y	0.7275	likely_pathogenic	0.7491	pathogenic	-1.531	Destabilizing	0.944	D	0.747	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.