TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15230	45913;45914;45915	chr2:178620922;178620921;178620920	chr2:179485649;179485648;179485647
N2AB	13589	40990;40991;40992	chr2:178620922;178620921;178620920	chr2:179485649;179485648;179485647
N2A	12662	38209;38210;38211	chr2:178620922;178620921;178620920	chr2:179485649;179485648;179485647
N2B	6165	18718;18719;18720	chr2:178620922;178620921;178620920	chr2:179485649;179485648;179485647
Novex-1	6290	19093;19094;19095	chr2:178620922;178620921;178620920	chr2:179485649;179485648;179485647
Novex-2	6357	19294;19295;19296	chr2:178620922;178620921;178620920	chr2:179485649;179485648;179485647
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-104
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2504
• 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
E/G	rs1209787066	-1.61	1.0	D	0.747	0.603	0.607256217586	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
E/G	rs1209787066	-1.61	1.0	D	0.747	0.603	0.607256217586	gnomAD-4.0.0	3.1879E-06	None	None	None	None	N	None	0	2.29263E-05	None	0	0	None	0	0	0	0	3.03122E-05

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
E/A	0.3633	ambiguous	0.3354	benign	-0.979	Destabilizing	0.999	D	0.663	neutral	D	0.611650359	None	None	N
E/C	0.9761	likely_pathogenic	0.9615	pathogenic	-0.608	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
E/D	0.6443	likely_pathogenic	0.6577	pathogenic	-1.341	Destabilizing	0.999	D	0.463	neutral	D	0.673812746	None	None	N
E/F	0.9513	likely_pathogenic	0.9364	pathogenic	-0.467	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
E/G	0.6514	likely_pathogenic	0.5762	pathogenic	-1.38	Destabilizing	1.0	D	0.747	deleterious	D	0.676006104	None	None	N
E/H	0.8244	likely_pathogenic	0.8044	pathogenic	-0.746	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/I	0.6478	likely_pathogenic	0.594	pathogenic	0.139	Stabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
E/K	0.3122	likely_benign	0.2717	benign	-1.03	Destabilizing	0.999	D	0.551	neutral	N	0.503218333	None	None	N
E/L	0.7793	likely_pathogenic	0.7398	pathogenic	0.139	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/M	0.7282	likely_pathogenic	0.6834	pathogenic	0.652	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/N	0.7527	likely_pathogenic	0.7393	pathogenic	-1.411	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/P	0.9891	likely_pathogenic	0.9855	pathogenic	-0.213	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Q	0.246	likely_benign	0.2371	benign	-1.223	Destabilizing	1.0	D	0.615	neutral	D	0.592435225	None	None	N
E/R	0.5178	ambiguous	0.4519	ambiguous	-0.791	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/S	0.5308	ambiguous	0.5137	ambiguous	-1.862	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	N
E/T	0.4854	ambiguous	0.4536	ambiguous	-1.521	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
E/V	0.4293	ambiguous	0.3903	ambiguous	-0.213	Destabilizing	1.0	D	0.777	deleterious	D	0.555001522	None	None	N
E/W	0.9895	likely_pathogenic	0.9857	pathogenic	-0.335	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
E/Y	0.9346	likely_pathogenic	0.9213	pathogenic	-0.236	Destabilizing	1.0	D	0.796	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.