TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6115	18568;18569;18570	chr2:178729910;178729909;178729908	chr2:179594637;179594636;179594635
N2AB	5798	17617;17618;17619	chr2:178729910;178729909;178729908	chr2:179594637;179594636;179594635
N2A	4871	14836;14837;14838	chr2:178729910;178729909;178729908	chr2:179594637;179594636;179594635
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: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-45
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.3274
• 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
L/F	rs771329302	None	0.317	N	0.61	0.129	0.460795861206	gnomAD-4.0.0	2.73784E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59839E-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
L/A	0.1155	likely_benign	0.1286	benign	-0.46	Destabilizing	0.035	N	0.669	neutral	None	None	None	None	N
L/C	0.411	ambiguous	0.4213	ambiguous	-0.781	Destabilizing	0.824	D	0.705	prob.neutral	None	None	None	None	N
L/D	0.4203	ambiguous	0.4595	ambiguous	-0.313	Destabilizing	0.38	N	0.752	deleterious	None	None	None	None	N
L/E	0.1725	likely_benign	0.1982	benign	-0.398	Destabilizing	0.149	N	0.74	deleterious	None	None	None	None	N
L/F	0.0921	likely_benign	0.0959	benign	-0.591	Destabilizing	0.317	N	0.61	neutral	N	0.506590593	None	None	N
L/G	0.3633	ambiguous	0.3937	ambiguous	-0.565	Destabilizing	0.149	N	0.713	prob.delet.	None	None	None	None	N
L/H	0.1309	likely_benign	0.1493	benign	0.105	Stabilizing	0.935	D	0.761	deleterious	None	None	None	None	N
L/I	0.0669	likely_benign	0.0654	benign	-0.298	Destabilizing	None	N	0.521	neutral	N	0.462298311	None	None	N
L/K	0.1614	likely_benign	0.1827	benign	-0.371	Destabilizing	0.149	N	0.71	prob.delet.	None	None	None	None	N
L/M	0.0874	likely_benign	0.0888	benign	-0.641	Destabilizing	0.38	N	0.639	neutral	None	None	None	None	N
L/N	0.2522	likely_benign	0.2775	benign	-0.247	Destabilizing	0.38	N	0.753	deleterious	None	None	None	None	N
L/P	0.4325	ambiguous	0.5299	ambiguous	-0.324	Destabilizing	0.555	D	0.767	deleterious	None	None	None	None	N
L/Q	0.0942	likely_benign	0.1088	benign	-0.421	Destabilizing	0.555	D	0.75	deleterious	None	None	None	None	N
L/R	0.1103	likely_benign	0.1262	benign	0.093	Stabilizing	0.555	D	0.748	deleterious	None	None	None	None	N
L/S	0.1412	likely_benign	0.1554	benign	-0.61	Destabilizing	0.005	N	0.591	neutral	N	0.446619569	None	None	N
L/T	0.0948	likely_benign	0.1041	benign	-0.597	Destabilizing	0.002	N	0.601	neutral	None	None	None	None	N
L/V	0.0623	likely_benign	0.0623	benign	-0.324	Destabilizing	None	N	0.429	neutral	N	0.431665973	None	None	N
L/W	0.1602	likely_benign	0.1753	benign	-0.616	Destabilizing	0.935	D	0.742	deleterious	None	None	None	None	N
L/Y	0.2147	likely_benign	0.2321	benign	-0.385	Destabilizing	0.555	D	0.711	prob.delet.	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.