TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15374	46345;46346;46347	chr2:178620401;178620400;178620399	chr2:179485128;179485127;179485126
N2AB	13733	41422;41423;41424	chr2:178620401;178620400;178620399	chr2:179485128;179485127;179485126
N2A	12806	38641;38642;38643	chr2:178620401;178620400;178620399	chr2:179485128;179485127;179485126
N2B	6309	19150;19151;19152	chr2:178620401;178620400;178620399	chr2:179485128;179485127;179485126
Novex-1	6434	19525;19526;19527	chr2:178620401;178620400;178620399	chr2:179485128;179485127;179485126
Novex-2	6501	19726;19727;19728	chr2:178620401;178620400;178620399	chr2:179485128;179485127;179485126
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-105
• Domain position: 73
• Structural Position: 157
• Q(SASA): 0.2838
• 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
T/A	rs1313103090	None	0.024	N	0.431	0.09	0.236278675362	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs1313103090	None	0.024	N	0.431	0.09	0.236278675362	gnomAD-4.0.0	6.58293E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47267E-05	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
T/A	0.1102	likely_benign	0.1044	benign	-1.008	Destabilizing	0.024	N	0.431	neutral	N	0.49237478	None	None	N
T/C	0.3981	ambiguous	0.4172	ambiguous	-0.73	Destabilizing	0.628	D	0.505	neutral	None	None	None	None	N
T/D	0.4589	ambiguous	0.415	ambiguous	-0.768	Destabilizing	0.136	N	0.531	neutral	None	None	None	None	N
T/E	0.2681	likely_benign	0.2629	benign	-0.701	Destabilizing	0.136	N	0.509	neutral	None	None	None	None	N
T/F	0.2522	likely_benign	0.2318	benign	-0.813	Destabilizing	None	N	0.486	neutral	None	None	None	None	N
T/G	0.3835	ambiguous	0.3651	ambiguous	-1.336	Destabilizing	0.136	N	0.546	neutral	None	None	None	None	N
T/H	0.2424	likely_benign	0.2431	benign	-1.55	Destabilizing	0.214	N	0.535	neutral	None	None	None	None	N
T/I	0.1534	likely_benign	0.1485	benign	-0.198	Destabilizing	None	N	0.289	neutral	N	0.424500793	None	None	N
T/K	0.2185	likely_benign	0.2215	benign	-0.877	Destabilizing	0.072	N	0.51	neutral	None	None	None	None	N
T/L	0.1186	likely_benign	0.1117	benign	-0.198	Destabilizing	0.002	N	0.365	neutral	None	None	None	None	N
T/M	0.0897	likely_benign	0.0901	benign	0.026	Stabilizing	0.007	N	0.372	neutral	None	None	None	None	N
T/N	0.1699	likely_benign	0.1503	benign	-1.026	Destabilizing	0.295	N	0.539	neutral	N	0.49262601	None	None	N
T/P	0.5266	ambiguous	0.5065	ambiguous	-0.435	Destabilizing	0.56	D	0.531	neutral	N	0.514037374	None	None	N
T/Q	0.2131	likely_benign	0.2155	benign	-1.102	Destabilizing	0.356	N	0.535	neutral	None	None	None	None	N
T/R	0.1807	likely_benign	0.1772	benign	-0.74	Destabilizing	0.356	N	0.531	neutral	None	None	None	None	N
T/S	0.1441	likely_benign	0.1319	benign	-1.304	Destabilizing	0.055	N	0.523	neutral	N	0.479640412	None	None	N
T/V	0.13	likely_benign	0.1293	benign	-0.435	Destabilizing	None	N	0.279	neutral	None	None	None	None	N
T/W	0.5431	ambiguous	0.5406	ambiguous	-0.777	Destabilizing	0.676	D	0.531	neutral	None	None	None	None	N
T/Y	0.2728	likely_benign	0.2626	benign	-0.528	Destabilizing	None	N	0.494	neutral	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.