TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6129	18610;18611;18612	chr2:178729868;178729867;178729866	chr2:179594595;179594594;179594593
N2AB	5812	17659;17660;17661	chr2:178729868;178729867;178729866	chr2:179594595;179594594;179594593
N2A	4885	14878;14879;14880	chr2:178729868;178729867;178729866	chr2:179594595;179594594;179594593
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: ATA
• RefSeq wild type template codon: TAT
• Domain: Ig-45
• Domain position: 25
• Structural Position: 35
• Q(SASA): 0.1085
• 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	rs2080081483	None	None	N	0.215	0.066	0.223847106136	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs2080081483	None	None	N	0.215	0.066	0.223847106136	gnomAD-4.0.0	2.02988E-06	None	None	None	None	N	None	3.49406E-05	0	None	0	0	None	0	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	0.8083	likely_pathogenic	0.7448	pathogenic	-2.288	Highly Destabilizing	0.035	N	0.666	neutral	None	None	None	None	N
I/C	0.9092	likely_pathogenic	0.8819	pathogenic	-1.456	Destabilizing	0.824	D	0.751	deleterious	None	None	None	None	N
I/D	0.9914	likely_pathogenic	0.9867	pathogenic	-2.459	Highly Destabilizing	0.555	D	0.824	deleterious	None	None	None	None	N
I/E	0.9762	likely_pathogenic	0.9666	pathogenic	-2.18	Highly Destabilizing	0.555	D	0.809	deleterious	None	None	None	None	N
I/F	0.3354	likely_benign	0.3237	benign	-1.302	Destabilizing	0.235	N	0.769	deleterious	None	None	None	None	N
I/G	0.956	likely_pathogenic	0.9436	pathogenic	-2.881	Highly Destabilizing	0.555	D	0.806	deleterious	None	None	None	None	N
I/H	0.9676	likely_pathogenic	0.9572	pathogenic	-2.458	Highly Destabilizing	0.935	D	0.793	deleterious	None	None	None	None	N
I/K	0.9584	likely_pathogenic	0.9421	pathogenic	-1.48	Destabilizing	0.484	N	0.81	deleterious	D	0.527530969	None	None	N
I/L	0.1465	likely_benign	0.1366	benign	-0.55	Destabilizing	None	N	0.24	neutral	D	0.527501796	None	None	N
I/M	0.1643	likely_benign	0.147	benign	-0.589	Destabilizing	0.317	N	0.714	prob.delet.	N	0.520440625	None	None	N
I/N	0.91	likely_pathogenic	0.869	pathogenic	-1.955	Destabilizing	0.791	D	0.826	deleterious	None	None	None	None	N
I/P	0.9832	likely_pathogenic	0.9787	pathogenic	-1.113	Destabilizing	0.791	D	0.825	deleterious	None	None	None	None	N
I/Q	0.9607	likely_pathogenic	0.9455	pathogenic	-1.7	Destabilizing	0.791	D	0.819	deleterious	None	None	None	None	N
I/R	0.9435	likely_pathogenic	0.9208	pathogenic	-1.47	Destabilizing	0.484	N	0.826	deleterious	D	0.527530969	None	None	N
I/S	0.8961	likely_pathogenic	0.8559	pathogenic	-2.673	Highly Destabilizing	0.38	N	0.784	deleterious	None	None	None	None	N
I/T	0.7921	likely_pathogenic	0.7293	pathogenic	-2.231	Highly Destabilizing	0.062	N	0.716	prob.delet.	N	0.499258497	None	None	N
I/V	0.0825	likely_benign	0.0834	benign	-1.113	Destabilizing	None	N	0.215	neutral	N	0.411434268	None	None	N
I/W	0.9646	likely_pathogenic	0.959	pathogenic	-1.704	Destabilizing	0.935	D	0.795	deleterious	None	None	None	None	N
I/Y	0.8405	likely_pathogenic	0.8187	pathogenic	-1.376	Destabilizing	0.555	D	0.789	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.