TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15368	46327;46328;46329	chr2:178620419;178620418;178620417	chr2:179485146;179485145;179485144
N2AB	13727	41404;41405;41406	chr2:178620419;178620418;178620417	chr2:179485146;179485145;179485144
N2A	12800	38623;38624;38625	chr2:178620419;178620418;178620417	chr2:179485146;179485145;179485144
N2B	6303	19132;19133;19134	chr2:178620419;178620418;178620417	chr2:179485146;179485145;179485144
Novex-1	6428	19507;19508;19509	chr2:178620419;178620418;178620417	chr2:179485146;179485145;179485144
Novex-2	6495	19708;19709;19710	chr2:178620419;178620418;178620417	chr2:179485146;179485145;179485144
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-105
• Domain position: 67
• Structural Position: 151
• Q(SASA): 0.2638
• 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/A	None	None	0.999	N	0.684	0.553	0.464442853059	gnomAD-4.0.0	1.59442E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86418E-06	0	0
E/K	None	None	0.999	D	0.591	0.445	0.479893544335	gnomAD-4.0.0	1.59446E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86428E-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
E/A	0.4414	ambiguous	0.4158	ambiguous	-0.956	Destabilizing	0.999	D	0.684	prob.neutral	N	0.500368154	None	None	N
E/C	0.9741	likely_pathogenic	0.9748	pathogenic	-0.486	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/D	0.7895	likely_pathogenic	0.7632	pathogenic	-1.106	Destabilizing	0.999	D	0.52	neutral	D	0.548296432	None	None	N
E/F	0.9793	likely_pathogenic	0.974	pathogenic	-0.251	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/G	0.6127	likely_pathogenic	0.5864	pathogenic	-1.352	Destabilizing	1.0	D	0.774	deleterious	D	0.549363348	None	None	N
E/H	0.9423	likely_pathogenic	0.9212	pathogenic	-0.469	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/I	0.8492	likely_pathogenic	0.7898	pathogenic	0.137	Stabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
E/K	0.5422	ambiguous	0.416	ambiguous	-0.624	Destabilizing	0.999	D	0.591	neutral	D	0.532895693	None	None	N
E/L	0.9119	likely_pathogenic	0.8784	pathogenic	0.137	Stabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
E/M	0.8533	likely_pathogenic	0.8061	pathogenic	0.628	Stabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
E/N	0.8788	likely_pathogenic	0.8531	pathogenic	-1.215	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/P	0.9934	likely_pathogenic	0.9921	pathogenic	-0.207	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
E/Q	0.3922	ambiguous	0.3208	benign	-1.045	Destabilizing	1.0	D	0.633	neutral	N	0.516057993	None	None	N
E/R	0.6834	likely_pathogenic	0.587	pathogenic	-0.316	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/S	0.6611	likely_pathogenic	0.629	pathogenic	-1.559	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
E/T	0.6936	likely_pathogenic	0.6184	pathogenic	-1.219	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/V	0.7178	likely_pathogenic	0.6286	pathogenic	-0.207	Destabilizing	1.0	D	0.847	deleterious	D	0.53549795	None	None	N
E/W	0.9952	likely_pathogenic	0.9936	pathogenic	0.054	Stabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/Y	0.9666	likely_pathogenic	0.9541	pathogenic	0.026	Stabilizing	1.0	D	0.855	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.